From stem cells to bone: Phenotype acquisition, stabilization, and tissue engineering in animal models

ILAR Journal

Volumn 51, Issue 1, 2010, Pages 42-61

  Gordeladze, Jan O ^a,b,c   Reseland, Janne E ^d   Duroux Richard, Isabelle ^b   Apparailly, Florence ^b   Jorgensen, Christian ^b,e  

^a UNIVERSITY OF OSLO   (Norway)

^b INSERM   (France)

^c UNIV MONTPELLIER   (France)

^d UNIVERSITY OF OSLO   (Norway)

^e LAPEYRONIE HOSPITAL   (France)

Author keywords

Animal models; Growth factors; Mechanostimulation; MicroRNAs; Osteoblasts; Scaffolds; Stem cells; Transcription factors

Indexed keywords

EID: 77955759577     PISSN: 10842020     EISSN: None     Source Type: Journal    
DOI: 10.1093/ilar.51.1.42     Document Type: Review

References (254)

1. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, Kos CH, Pollak MR, Brown EM, Scadden DT. 2006. Stem cell engraftment at the endosteal niche is specified by the calciumsensing receptor. Nature 439:599-603.
2. Aguda BD, Kim Y, Piper-Hunter MG, Friedman A, Marsh CB. 2008. MicroRNA regulation of a cancer network: Consequences of the feedback loops involving mir-17-92, e2f, and myc. Proc Natl Acad Sci U S A 105:19678-19683.
3. Ammann P, Bonjour JP, Rizzoli R. 2000. Essential amino acid supplements increase muscle weight, bone mass and bone strength in adult osteoporotic rats. J Musculoskelet Neuronal Interact 1:43-44.
4. Ammann P, Laib A, Bonjour JP, Meyer JM, Ruegsegger P, Rizzoli R. 2002. Dietary essential amino acid supplements increase bone strength by infl uencing bone mass and bone microarchitecture in ovariectomized adult rats fed an isocaloric low-protein diet. J Bone Miner Res 17:1264-1272.
5. Anderson RG. 1998. The caveolae membrane system. Annu Rev Biochem 67:199-225.
6. Annalisa P, Furio P, Ilaria Z, Anna A, Luca S, Marcella M, Marzia A, Elena M, Carinci F. 2008. Anorganic bovine bone and a silicate-based synthetic bone activate different microRNAs. J Oral Sci 50:301-307.
7. Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Koh GY, Suda T. 2004. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149-161.
8. Armstrong VJ, Muzylak M, Sunters A, Zaman G, Saxon LK, Price JS, Lanyon LE. 2007. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem 282:20715-20727.
9. Axelrad TW, Kakar S, Einhorn TA. 2007. New technologies for the enhancement of skeletal repair. Injury 38 Suppl 1:S49-S62.
10. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. 2002. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42-48.
11. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL. 2005. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: A novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577-4583.
12. Bendall AJ, Abate-Shen C. 2000. Roles for msx and dlx homeoproteins in vertebrate development. Gene 247:17-31.
13. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, Wu H, Yu K, Ornitz DM, Olson EN, Justice MJ, Karsenty G. 2004. A Twist code determines the onset of osteoblast differentiation. Dev Cell 6:423-435.
14. Bonewald LF, Johnson ML. 2008. Osteocytes, mechanosensing and Wnt signaling. Bone 42:606-615.
15. Boutahar N, Guignandon A, Vico L, Lafage-Proust MH. 2004. Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activation. J Biol Chem 279:30588-30599.
16. Brosh R, Shalgi R, Liran A, Landan G, Korotayev K, Nguyen GH, Enerly E, Johnsen H, Buganim Y, Solomon H, Goldstein I, Madar S, Goldfinger N, Borresen-Dale AL, Ginsberg D, Harris CC, Pilpel Y, Oren M, Rotter V. 2008. P53-repressed miRNAs are involved with e2f in a feed-forward loop promoting proliferation. Mol Syst Biol 4:229.
17. Brown BD, Gentner B, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L. 2007. Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol 25:1457-1467.
18. Bruder SP, Kraus KH, Goldberg VM, Kadiyala S. 1998. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg Am 80:985-996.
19. Byers BA, Guldberg RE, Garcia AJ. 2004. Synergy between genetic and tissue engineering: Runx2 overexpression and in vitro construct development enhance in vivo mineralization. Tissue Eng 10:1757-1766.
20. Byers BA, Guldberg RE, Hutmacher DW, Garcia AJ. 2006. Effects of runx2 genetic engineering and in vitro maturation of tissue-engineered constructs on the repair of critical size bone defects. J Biomed Mater Res A 76:646-655.
21. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT. 2003. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841-846.
22. Canalis E. 2008. Notch signaling in osteoblasts. Sci Signal 1:pe17.
23. Cancedda R, Giannoni P, Mastrogiacomo M. 2007. A tissue engineering approach to bone repair in large animal models and in clinical practice. Biomaterials 28:4240-4250.
24. Carinci F, Piattelli A, Degidi M, Palmieri A, Perrotti V, Scapoli L, Martinelli M, Zuccarino L, Pezzetti F. 2007. Effects of demineralized freeze-dried bone allograft on gene expression of osteoblastlike mg63 cells. Int J Periodontics Restorative Dent 27:596-601.
25. Carrier RL, Rupnick M, Langer R, Schoen FJ, Freed LE, Vunjak-Novakovic G. 2002. Perfusion improves tissue architecture of engineered cardiac muscle. Tissue Eng 8:175-188.
26. Carthew RW, Sontheimer EJ. 2009. Origins and mechanisms of miRNAs and siRNAs. Cell 136:642-655.
27. Carvalho RS, Scott JE, Suga DM, Yen EH. 1994. Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone. J Bone Miner Res 9:999-1011.
28. Castillo AB, Alam I, Tanaka SM, Levenda J, Li J, Warden SJ, Turner CH. 2006. Low-amplitude, broad-frequency vibration effects on cortical bone formation in mice. Bone 39:1087-1096.
29. Celil AB, Hollinger JO, Campbell PG. 2005. Osx transcriptional regulation is mediated by additional pathways to bmp2/smad signaling. J Cell Biochem 95:518-528.
30. Chaudhary LR, Hofmeister AM, Hruska KA. 2004. Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone 34:402-411.
31. Chen NX, Ryder KD, Pavalko FM, Turner CH, Burr DB, Qiu J, Duncan RL. 2000. Ca(2+) regulates fl uid shear-induced cytoskeletal reorganization and gene expression in osteoblasts. Am J Physiol Cell Physiol 278:C989-C997.
32. Chen TL. 2004. Inhibition of growth and differentiation of osteoprogenitors in mouse bone marrow stromal cell cultures by increased donor age and glucocorticoid treatment. Bone 35:83-95.
33. Cherian PP, Siller-Jackson AJ, Gu S, Wang X, Bonewald LF, Sprague E, Jiang JX. 2005. Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin. Mol Biol Cell 16:3100-3106.
34. Christensen JL, Weissman IL. 2001. Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells. Proc Natl Acad Sci U S A 98:14541-14546.
35. Christiansen BA, Silva MJ. 2006. The effect of varying magnitudes of whole body vibration on several skeletal sites in mice. Ann Biomed Eng 34:1149-1156.
36. Coura Rdos S, Nardi NB. 2007. The state of the art of adeno-associated virus-based vectors in gene therapy. Virol J 4:99.
37. Cyster JG. 2005. Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu Rev Immunol 23:127-159.
38. Czerwiński E, Badurski JE, Marcinowska-Suchowierska E, Osieleniec J. 2007. Current understanding of osteoporosis according to the position of the World Health Organization (WHO) and International Osteoporosis Foundation. Ortop Traumatol Rehabil 9:337-356.
39. Dassouli A, Sulpice JC, Roux S, Crozatier B. 1993. Stretch-induced inositol trisphosphate and tetrakisphosphate production in rat cardiomyocytes. J Mol Cell Cardiol 25:973-982.
40. Davidson RM, Tatakis DW, Auerbach AL. 1990. Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pfl ugers Arch 416:646-651.
41. Day TF, Guo X, Garrett-Beal L, Yang Y. 2005. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739-750.
42. De Smet E, Jaecques SV, Wevers M, Jansen JA, Jacobs R, Sloten JV, Naert IE. 2006. Effect of controlled early implant loading on bone healing and bone mass in guinea pigs, as assessed by micro-CT and histology. Eur J Oral Sci 114:232-242.
43. De Smet E, Jaecques SV, Jansen JJ, Walboomers F, Vander Sloten J, Naert IE. 2007. Effect of constant strain rate, composed of varying amplitude and frequency, of early loading on peri-implant bone (re)modeling. J Clin Periodontol 34:618-624.
44. Dean RM, Bishop MR. 2003. Graft-versus-host disease: Emerging concepts in prevention and therapy. Curr Hematol Rep 2:287-294.
45. Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, Karsenty G, Grosschedl R. 2006. Satb2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 125:971-986.
46. Donahue HJ. 2000. Gap junctions and biophysical regulation of bone cell differentiation. Bone 26:417-422.
47. Driessen RL, Johnston HM, Nilsson SK. 2003. Membrane-bound stem cell factor is a key regulator in the initial lodgment of stem cells within the endosteal marrow region. Exp Hematol 31:1284-1291.
48. Drosse I, Volkmer E, Capanna R, De Biase P, Mutschler W, Schieker M. 2008. Tissue engineering for bone defect healing: An update on a multicomponent approach. Injury 39 Suppl 2:S9-S20.
49. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. 1997. Osf2/cbfa1: A transcriptional activator of osteoblast differentiation. Cell 89:747-754.
50. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. 2000. Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass. Cell 100:197-207.
51. Fan X, Roy E, Zhu L, Murphy TC, Ackert-Bicknell C, Hart CM, Rosen C, Nanes MS, Rubin J. 2004. Nitric oxide regulates receptor activator of nuclear factor-kappab ligand and osteoprotegerin expression in bone marrow stromal cells. Endocrinology 145:751-759.
52. Flieger J, Karachalios T, Khaldi L, Raptou P, Lyritis G. 1998. Mechanical stimulation in the form of vibration prevents postmenopausal bone loss in ovariectomized rats. Calcif Tissue Int 63:510-514.
53. Flynt AS, Lai EC. 2008. Biological principles of microRNA-mediated regulation: Shared themes amid diversity. Nat Rev Genet 9:831-842.
54. Fritz V, Noel D, Bouquet C, Opolon P, Voide R, Apparailly F, Louis-Plence P, Bouffi C, Drissi H, Xie C, Perricaudet M, Muller R, Schwarz E, Jorgensen C. 2008. Antitumoral activity and osteogenic potential of mesenchymal stem cells expressing the urokinase-type plasminogen antagonist amino-terminal fragment in a murine model of osteolytic tumor. Stem Cells 26:2981-2990.
55. Frost HM. 2003a. Bone's mechanostat: A 2003 update. Anat Rec A Discov Mol Cell Evol Biol 275:1081-1101.
56. Frost HM. 2003b. New targets for fascial, ligament and tendon research: A perspective from the Utah paradigm of skeletal physiology. J Musculoskelet Neuronal Interact 3:201-209.
57. Frost HM. 2004. A 2003 update of bone physiology and Wolff's law for clinicians. Angle Orthod 74:3-15.
58. Fuchs S, Ghanaati S, Orth C, Barbeck M, Kolbe M, Hofmann A, Eblenkamp M, Gomes M, Reis RL, Kirkpatrick CJ. 2009. Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds. Biomaterials 30:526-534.
59. Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K, Komori T. 2004. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with pi3k-akt signaling. J Cell Biol 166:85-95.
60. Galler KM, Cavender A, Yuwono V, Dong H, Shi S, Schmalz G, Hartgerink JD, D'Souza RN. 2008. Self-assembling peptide amphiphile nanofibers as a scaffold for dental stem cells. Tissue Eng Part A 14:2051-2058.
61. Garman R, Gaudette G, Donahue LR, Rubin C, Judex S. 2007. Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation. J Orthop Res 25:732-740.
62. Garzón-Muvdi T, Quiñones-Hinojosa A. 2010. Neural stem cell niches and homing: Recruitment and integration into functional tissues. ILAR J 51:3-23.
63. Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB. 2005. Canonical Wnt signaling promotes osteogenesis by directly stimulating runx2 gene expression. J Biol Chem 280:33132-33140.
64. Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. 2006. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res 21:1464-1474.
65. Glass DA 2nd, Karsenty G. 2006. Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway. Curr Top Dev Biol 73:43-84.
66. Glass DA 2nd, Karsenty G. 2007. In vivo analysis of Wnt signaling in bone. Endocrinology 148:2630-2634.
67. Gordeladze JO, Reseland JE. 2003. A unified model for the action of leptin on bone turnover. J Cell Biochem 88:706-712.
68. Gordeladze JO, Reseland JE, Drevon CA. 2001. Pharmacological interference with transcriptional control of osteoblasts: A possible role for leptin and fatty acids in maintaining bone strength and body lean mass. Curr Pharm Des 7:275-290.
69. Gordeladze JO, Drevon CA, Syversen U, Reseland JE. 2002. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: Impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem 85:825-836.
70. Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA. 2006. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 441:537-541.
71. Gudi S, Huvar I, White CR, McKnight NL, Dusserre N, Boss GR, Frangos JA. 2003. Rapid activation of ras by fl uid fl ow is mediated by galpha(q) and gbetagamma subunits of heterotrimeric G proteins in human endothelial cells. Arterioscler Thromb Vasc Biol 23:994-1000.
72. Guenou H, Kaabeche K, Mee SL, Marie PJ. 2005. A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome. Hum Mol Genet 14:1429-1439.
73. Guenou H, Kaabeche K, Dufour C, Miraoui H, Marie PJ. 2006. Downregulation of ubiquitin ligase cbl induced by twist haploinsufficiency in Saethre-Chotzen syndrome results in increased pi3k/akt signaling and osteoblast proliferation. Am J Pathol 169:1303-1311.
74. Guidobono F, Pagani F, Sibilia V, Netti C, Lattuada N, Rapetti D, Mrak E, Villa I, Cavani F, Bertoni L, Palumbo C, Ferretti M, Marotti G, Rubinacci A. 2006. Different skeletal regional response to continuous brain infusion of leptin in the rat. Peptides 27:1426-1433.
75. Gusi N, Raimundo A, Leal A. 2006. Low-frequency vibratory exercise reduces the risk of bone fracture more than walking: A randomized controlled trial. BMC Musculoskelet Disord 7:92.
76. Gutierrez S, Javed A, Tennant DK, van Rees M, Montecino M, Stein GS, Stein JL, Lian JB. 2002. Ccaat/enhancer-binding proteins (C/EBP) beta and delta activate osteocalcin gene transcription and synergize with runx2 at the C/EBP element to regulate bone-specific expression. J Biol Chem 277:1316-1323.
77. Hassan MQ, Javed A, Morasso MI, Karlin J, Montecino M, van Wijnen AJ, Stein GS, Stein JL, Lian JB. 2004. Dlx3 transcriptional regulation of osteoblast differentiation: Temporal recruitment of msx2, dlx3, and dlx5 homeodomain proteins to chromatin of the osteocalcin gene. Mol Cell Biol 24:9248-9261.
78. Hassan MQ, Tare R, Lee SH, Mandeville M, Weiner B, Montecino M, van Wijnen AJ, Stein JL, Stein GS, Lian JB. 2007. Hoxa10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes. Mol Cell Biol 27:3337-3352.
79. Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S. 2002. Recruitment of stem and progenitor cells from the bone marrow niche requires mmp-9 mediated release of kit-ligand. Cell 109:625-637.
80. Hernandez CJ, Keaveny TM. 2006. A biomechanical perspective on bone quality. Bone 39:1173-1181.
81. Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C. 2005. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727-738.
82. Hinoi E, Fujimori S, Wang L, Hojo H, Uno K, Yoneda Y. 2006. Nrf2 negatively regulates osteoblast differentiation via interfering with runx2-dependent transcriptional activation. J Biol Chem 281:18015-18024.
83. Hobert O. 2008. Gene regulation by transcription factors and microRNAs. Science 319:1785-1786.
84. Holleville N, Mateos S, Bontoux M, Bollerot K, Monsoro-Burq AH. 2007. Dlx5 drives runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. Dev Biol 304:860-874.
85. Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB. 2005. Taz, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309:1074-1078.
86. Hornstein E, Shomron N. 2006. Canalization of development by micrornas. Nat Genet 38 Suppl:S20-24.
87. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F. 2005a. Sequential roles of hedgehog and Wnt signaling in osteoblast development. Development 132:49-60.
88. Hu Z, Peel SA, Ho SK, Sandor GK, Clokie CM. 2005b. Role of bovine bone morphogenetic proteins in bone matrix protein and osteoblast-related gene expression during rat bone marrow stromal cell differentiation. J Craniofac Surg 16:1006-1014.
89. Huang CK, Huang W, Zuk P, Jarrahy R, Rudkin GH, Ishida K, Yamaguchi DT, Miller TA. 2008. Genetic markers of osteogenesis and angiogenesis are altered in processed lipoaspirate cells when cultured on threedimensional scaffolds. Plast Reconstr Surg 121:411-423.
90. Ishida T, Peterson TE, Kovach NL, Berk BC. 1996. Map kinase activation by fl ow in endothelial cells: Role of beta 1 integrins and tyrosine kinases. Circ Res 79:310-316.
91. Ishii M, Egen JG, Klauschen F, Meier-Schellersheim M, Saeki Y, Vacher J, Proia RL, Germain RN. 2009. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458: 524-528.
92. Iwamoto J, Takeda T, Sato Y, Uzawa M. 2005. Effect of whole body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate. Aging Clin Exp Res 17:157-163.
93. Jalali S, Li YS, Sotoudeh M, Yuan S, Li S, Chien S, Shyy JY. 1998. Shear stress activates p60src-ras-mapk signaling pathways in vascular endothelial cells. Arterioscler Thromb Vasc Biol 18:227-234.
94. Janmey PA, McCulloch CA. 2007. Cell mechanics: Integrating cell responses to mechanical stimuli. Annu Rev Biomed Eng 9:1-34.
95. Jee WS. 2005. The past, present, and future of bone morphometry: Its contribution to an improved understanding of bone biology. J Bone Miner Metab 23 Suppl:1-10.
96. Jee WS. 2006. Harold M. Frost, MD, DSc (Hon) -- One man's association. J Musculoskelet Neuronal Interact 6:113-121.
97. Jheon AH, Ganss B, Cheifetz S, Sodek J. 2001. Characterization of a novel krab/c2h2 zinc finger transcription factor involved in bone development. J Biol Chem 276:18282-18289.
98. Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH. 2006. Regulation of adult bone mass by the zinc finger adapter protein schnurri-3. Science 312:1223-1227.
99. Jorgensen C, Gordeladze J, Noel D. 2004. Tissue engineering through autologous mesenchymal stem cells. Curr Opin Biotechnol 15:406-410.
100. Judex S, Donahue LR, Rubin C. 2002. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J 16:1280-1282.
101. Judex S, Lei X, Han D, Rubin C. 2007. Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J Biomech 40:1333-1339.
102. Kanayama N, Fukushima S, Nishiyama N, Itaka K, Jang WD, Miyata K, Yamasaki Y, Chung UI, Kataoka K. 2006. A peg-based biocompatible block catiomer with high buffering capacity for the construction of polyplex micelles showing efficient gene transfer toward primary cells. Chem Med Chem 1:439-444.
103. Kaneps AJ, Stover SM, Lane NE. 1997. Changes in canine cortical and cancellous bone mechanical properties following immobilization and remobilization with exercise. Bone 21:419-423.
104. Kapur S, Baylink DJ, Lau KH. 2003. Fluid fl ow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32:241-251.
105. Karsenty G, Wagner EF. 2002. Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2:389-406.
106. Kaspar D, Seidl W, Neidlinger-Wilke C, Beck A, Claes L, Ignatius A. 2002. Proliferation of human-derived osteoblast-like cells depends on the cycle number and frequency of uniaxial strain. J Biomech 35:873-880.
107. Katsumi A, Orr AW, Tzima E, Schwartz MA. 2004. Integrins in mechanotransduction. J Biol Chem 279:12001-12004.
108. Kawamura S, Miyamoto S, Brown JH. 2003. Initiation and transduction of stretch-induced rhoa and rac1 activation through caveolae: Cytoskeletal regulation of erk translocation. J Biol Chem 278:31111-31117.
109. Keller H, Kneissel M. 2005. Sost is a target gene for PTH in bone. Bone 37:148-158.
110. Kelly EJ, Russell SJ. 2009. MicroRNAs and the regulation of vector tropism. Mol Ther 17:409-416.
111. Keramaris NC, Calori GM, Nikolaou VS, Schemitsch EH, Giannoudis PV. 2008. Fracture vascularity and bone healing: A systematic review of the role of VEGF. Injury 39 Suppl 2:S45-S57.
112. Khosla S, Westendorf JJ, Oursler MJ. 2008. Building bone to reverse osteoporosis and repair fractures. J Clin Invest 118:421-428.
113. Kim S, Koga T, Isobe M, Kern BE, Yokochi T, Chin YE, Karsenty G, Taniguchi T, Takayanagi H. 2003. Stat1 functions as a cytoplasmic attenuator of runx2 in the transcriptional program of osteoblast differentiation. Genes Dev 17:1979-1991.
114. Kim YJ, Kim BG, Lee SJ, Lee HK, Lee SH, Ryoo HM, Cho JY. 2007. The suppressive effect of myeloid elf-1-like factor (mef) in osteogenic differentiation. J Cell Physiol 211:253-260.
115. Klein-Nulend J, Helfrich MH, Sterck JG, MacPherson H, Joldersma M, Ralston SH, Semeins CM, Burger EH. 1998. Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent. Biochem Biophys Res Commun 250:108-114.
116. Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, Merkenschlager M, Kronenberg HM. 2008. Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A 105:1949-1954.
117. Koga T, Matsui Y, Asagiri M, Kodama T, de Crombrugghe B, Nakashima K, Takayanagi H. 2005. Nfat and osterix cooperatively regulate bone formation. Nat Med 11:880-885.
118. Komori T. 2006. Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99:1233-1239.
119. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. 1997. Targeted disruption of cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755-764.
120. Kon E, Muraglia A, Corsi A, Bianco P, Marcacci M, Martin I, Boyde A, Ruspantini I, Chistolini P, Rocca M, Giardino R, Cancedda R, Quarto R. 2000. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. J Biomed Mater Res 49:328-337.
121. Krishnan V, Bryant HU, Macdougald OA. 2006. Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202-1209.
122. Kumar S, Chanda D, Ponnazhagan S. 2008. Therapeutic potential of genetically modified mesenchymal stem cells. Gene Ther 15:711-715.
123. Lavandero S, Cartagena G, Guarda E, Corbalan R, Godoy I, Sapag-Hagar M, Jalil JE. 1993. Changes in cyclic AMP dependent protein kinase and active stiffness in the rat volume overload model of heart hypertrophy. Cardiovasc Res 27:1634-1638.
124. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O. 2003. Hla expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890-896.
125. Lecka-Czernik B, Gubrij I, Moerman EJ, Kajkenova O, Lipschitz DA, Manolagas SC, Jilka RL. 1999. Inhibition of osf2/cbfa1 expression and terminal osteoblast differentiation by ppargamma2. J Cell Biochem 74:357-371.
126. Lee JH, Rhie JW, Oh DY, Ahn ST. 2008. Osteogenic differentiation of human adipose tissue-derived stromal cells (HASCs) in a porous threedimensional scaffold. Biochem Biophys Res Commun 370:456-460.
127. Lee KS, Kim HJ, Li QL, Chi XZ, Ueta C, Komori T, Wozney JM, Kim EG, Choi JY, Ryoo HM, Bae SC. 2000. Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between runx2 and smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line c2c12. Mol Cell Biol 20:8783-8792.
128. Lee MH, Kim YJ, Yoon WJ, Kim JI, Kim BG, Hwang YS, Wozney JM, Chi XZ, Bae SC, Choi KY, Cho JY, Choi JY, Ryoo HM. 2005. Dlx5 specifically regulates runx2 type ii expression by binding to homeodomainresponse elements in the runx2 distal promoter. J Biol Chem 280:35579-35587.
129. Lee MS, Lowe GN, Strong DD, Wergedal JE, Glackin CA. 1999. Twist, a basic helix-loop-helix transcription factor, can regulate the human osteogenic lineage. J Cell Biochem 75:566-577.
130. Lee SH, Shin H. 2007. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv Drug Deliv Rev 59:339-359.
131. Levi G, Mantero S, Barbieri O, Cantatore D, Paleari L, Beverdam A, Genova F, Robert B, Merlo GR. 2006. Msx1 and dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of BMP signaling in palate formation. Mech Dev 123:3-16.
132. Li S, Chen BP, Azuma N, Hu YL, Wu SZ, Sumpio BE, Shyy JY, Chien S. 1999. Distinct roles for the small gtpases cdc42 and rho in endothelial responses to shear stress. J Clin Invest 103:1141-1150.
133. Li YJ, Batra NN, You L, Meier SC, Coe IA, Yellowley CE, Jacobs CR. 2004. Oscillatory fl uid fl ow affects human marrow stromal cell proliferation and differentiation. J Orthop Res 22:1283-1289.
134. Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM, Lian JB, Stein GS. 2008. A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci U S A 105:13906-13911.
135. Li Z, Hassan MQ, Jafferji M, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB. 2009. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284:15676-15684.
136. Lian JB, Stein GS. 2003. Runx2/cbfa1: A multifunctional regulator of bone formation. Curr Pharm Des 9:2677-2685.
137. Lian JB, Javed A, Zaidi SK, Lengner C, Montecino M, van Wijnen AJ, Stein JL, Stein GS. 2004. Regulatory controls for osteoblast growth and differentiation: Role of runx/cbfa/aml factors. Crit Rev Eukaryot Gene Expr 14:1-41.
138. Liebschner MA. 2004. Biomechanical considerations of animal models used in tissue engineering of bone. Biomaterials 25:1697-1714.
139. Liu G, Zhao L, Zhang W, Cui L, Liu W, Cao Y. 2008. Repair of goat tibial defects with bone marrow stromal cells and beta-tricalcium phosphate. J Mater Sci Mater Med 19:2367-2376.
140. Liu S, Calderwood DA, Ginsberg MH. 2000. Integrin cytoplasmic domainbinding proteins. J Cell Sci 113 (Pt 20):3563-3571.
141. Liu W, Toyosawa S, Furuichi T, Kanatani N, Yoshida C, Liu Y, Himeno M, Narai S, Yamaguchi A, Komori T. 2001. Overexpression of cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 155:157-166.
142. Liu W, Cui L, Cao Y. 2006. Bone reconstruction with bone marrow stromal cells. Methods Enzymol 420:362-380.
143. Liu YP, Haasnoot J, Berkhout B. 2007. Design of extended short hairpin RNAs for HIV-1 inhibition. Nucleic Acids Res 35:5683-5693.
144. Luan Y, Yu XP, Xu K, Ding B, Yu J, Huang Y, Yang N, Lengyel P, Di Cesare PE, Liu CJ. 2007. The retinoblastoma protein is an essential mediator of osteogenesis that links the p204 protein to the cbfa1 transcription factor thereby increasing its activity. J Biol Chem 282:16860-16870.
145. Manolagas SC, Almeida M. 2007. Gone with the Wnts: Beta-catenin, t-cell factor, forkhead box o, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism. Mol Endocrinol 21:2605-2614.
146. Marie PJ. 2008. Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys 473:98-105.
147. Martin RB. 2007. The importance of mechanical loading in bone biology and medicine. J Musculoskelet Neuronal Interact 7:48-53.
148. Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, Kanatani N, Moriishi T, Yamana K, Liu W, Kawaguchi H, Nakamura K, Komori T. 2007. Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Dev Dyn 236:1876-1890.
149. Mastrogiacomo M, Corsi A, Francioso E, Di Comite M, Monetti F, Scaglione S, Favia A, Crovace A, Bianco P, Cancedda R. 2006. Reconstruction of extensive long bone defects in sheep using resorbable bioceramics based on silicon stabilized tricalcium phosphate. Tissue Eng 12:1261-1273.
150. Matsumoto T, Kuroda R, Mifune Y, Kawamoto A, Shoji T, Miwa M, Asahara T, Kurosaka M. 2008. Circulating endothelial/skeletal progenitor cells for bone regeneration and healing. Bone 43:434-439.
151. McAllister TN, Frangos JA. 1999. Steady and transient fl uid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways. J Bone Miner Res 14:930-936.
152. McCarthy TL, &/x&&namegr type=editor&&name&&sname&Ji&/sname&&x& &/x&&fname&C&/fname&&/name&&/namegr&, Centrella M. 2000. Links among growth factors, hormones, and nuclear factors with essential roles in bone formation. Crit Rev Oral Biol Med 11:409-422.
153. McClelland RE, Coger RN. 2000. Use of micropathways to improve oxygen transport in a hepatic system. J Biomech Eng 122:268-273.
154. Mittra E, Rubin C, Qin YX. 2005. Interrelationship of trabecular mechanical and microstructural properties in sheep trabecular bone. J Biomech 38:1229-1237.
155. Mizuno S. 2005. A novel method for assessing effects of hydrostatic fl uid pressure on intracellular calcium: A study with bovine articular chondrocytes. Am J Physiol Cell Physiol 288:C329-C337.
156. Mizuno Y, Yagi K, Tokuzawa Y, Kanesaki-Yatsuka Y, Suda T, Katagiri T, Fukuda T, Maruyama M, Okuda A, Amemiya T, Kondoh Y, Tashiro H, Okazaki Y. 2008. Mir-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem Biophys Res Commun 368:267-272.
157. Morrison SJ, Weissman IL. 1994. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1:661-673.
158. Mulvihill BM, Prendergast PJ. 2008. An algorithm for bone mechanoresponsiveness: Implementation to study the effect of patient-specific cell mechanosensitivity on trabecular bone loss. Comput Methods Biomech Biomed Engin 11:443-451.
159. Muschler GF, Nakamoto C, Griffith LG. 2004. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am 86-A:1541-1558.
160. Nafei A, Danielsen CC, Linde F, Hvid I. 2000. Properties of growing trabecular ovine bone. Part I: Mechanical and physical properties. J Bone Joint Surg Br 82:910-920.
161. Newberry EP, Latifi T, Towler DA. 1998. Reciprocal regulation of osteocalcin transcription by the homeodomain proteins msx2 and dlx5. Biochemistry 37:16360-16368.
162. Niemeyer P, Krause U, Kasten P, Kreuz PC, Henle P, Sudkam NP, Mehlhorn A. 2006. Mesenchymal stem cell-based hla-independent cell therapy for tissue engineering of bone and cartilage. Curr Stem Cell Res Ther 1:21-27.
163. Nordsletten L. 2006. Recent developments in the use of bone morphogenetic protein in orthopaedic trauma surgery. Curr Med Res Opin 22 Suppl 1:S13-S17; S23.
164. Norvell SM, Alvarez M, Bidwell JP, Pavalko FM. 2004. Fluid shear stress induces beta-catenin signaling in osteoblasts. Calcif Tissue Int 75:396-404.
165. Okamoto T, Schlegel A, Scherer PE, Lisanti MP. 1998. Caveolins, a family of scaffolding proteins for organizing "Preassembled signaling complexes" at the plasma membrane. J Biol Chem 273:5419-5422.
166. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765-771.
167. Oxlund BS, Ortoft G, Andreassen TT, Oxlund H. 2003. Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats. Bone 32:69-77.
168. Oyajobi BO, Lomri A, Hott M, Marie PJ. 1999. Isolation and characterization of human clonogenic osteoblast progenitors immunoselected from fetal bone marrow stroma using stro-1 monoclonal antibody. J Bone Miner Res 14:351-361.
169. Ozcivici E, Garman R, Judex S. 2007. High-frequency oscillatory motions enhance the simulated mechanical properties of non-weight bearing trabecular bone. J Biomech 40:3404-3411.
170. Pagnotto MR, Wang Z, Karpie JC, Ferretti M, Xiao X, Chu CR. 2007. Adeno-associated viral gene transfer of transforming growth factorbeta1 to human mesenchymal stem cells improves cartilage repair. Gene Ther 14:804-813.
171. Palmieri A, Brunelli G, Guerzoni L, Lo Muzio L, Scarano A, Rubini C, Scapoli L, Martinelli M, Pezzetti F, Carinci F. 2007a. Comparison between titanium and anatase miRNAs regulation. Nanomedicine 3:138-143.
172. Palmieri A, Pezzetti F, Brunelli G, Zollino I, Scapoli L, Martinelli M, Arlotti M, Carinci F. 2007b. Differences in osteoblast miRNA induced by cell binding domain of collagen and silicate-based synthetic bone. J Biomed Sci 14:777-782.
173. Palmieri A, Pezzetti F, Brunelli G, Arlotti M, Lo Muzio L, Scarano A, Rubini C, Sollazzo V, Massari L, Carinci F. 2008. Anatase nanosurface regulates microRNAs. J Craniofac Surg 19:328-333.
174. Parhami F, Jackson SM, Tintut Y, Le V, Balucan JP, Territo M, Demer LL. 1999. Atherogenic diet and minimally oxidized low density lipoprotein inhibit osteogenic and promote adipogenic differentiation of marrow stromal cells. J Bone Miner Res 14:2067-2078.
175. Pearce AI, Richards RG, Milz S, Schneider E, Pearce SG. 2007. Animal models for implant biomaterial research in bone: A review. Eur Cell Mater 13:1-10.
176. Petite H, Viateau V, Bensaid W, Meunier A, de Pollak C, Bourguignon M, Oudina K, Sedel L, Guillemin G. 2000. Tissue-engineered bone regeneration. Nat Biotechnol 18:959-963.
177. Pike-Overzet K, de Ridder D, Weerkamp F, Baert MR, Verstegen MM, Brugman MH, Howe SJ, Reinders MJ, Thrasher AJ, Wagemaker G, van Dongen JJ, Staal FJ. 2006. Gene therapy: Is il2rg oncogenic in t-cell development? Nature 443:E5; discussion E6-E7.
178. Pogoda P, Egermann M, Schnell JC, Priemel M, Schilling AF, Alini M, Schinke T, Rueger JM, Schneider E, Clarke I, Amling M. 2006. Leptin inhibits bone formation not only in rodents, but also in sheep. J Bone Miner Res 21:1591-1599.
179. Ponader S, Brandt H, Vairaktaris E, von Wilmowsky C, Nkenke E, Schlegel KA, Neukam FW, Holst S, Muller FA, Greil P. 2008. In vitro response of hfob cells to pamidronate modified sodium silicate coated cellulose scaffolds. Colloids Surf B Biointerfaces 64:275-283.
180. Pratap J, Galindo M, Zaidi SK, Vradii D, Bhat BM, Robinson JA, Choi JY, Komori T, Stein JL, Lian JB, Stein GS, van Wijnen AJ. 2003. Cell growth regulatory role of runx2 during proliferative expansion of preosteoblasts. Cancer Res 63:5357-5362.
181. Prisby RD, Lafage-Proust MH, Malaval L, Belli A, Vico L. 2008. Effects of whole body vibration on the skeleton and other organ systems in man and animal models: What we know and what we need to know. Ageing Res Rev 7:319-329.
182. Raisz LG. 2005. Pathogenesis of osteoporosis: Concepts, confl icts, and prospects. J Clin Invest 115:3318-3325.
183. Rawlinson SC, Pitsillides AA, Lanyon LE. 1996. Involvement of different ion channels in osteoblasts' and osteocytes' early responses to mechanical strain. Bone 19:609-614.
184. Reichert JC, Saifzadeh S, Wullschleger ME, Epari DR, Schutz MA, Duda GN, Schell H, van Griensven M, Redl H, Hutmacher DW. 2009. The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 30:2149-2163.
185. Reseland JE, Gordeladze JO. 2002. Role of leptin in bone growth: Central player or peripheral supporter? FEBS Lett 528:40-42.
186. Reseland JE, Syversen U, Bakke I, Qvigstad G, Eide LG, Hjertner O, Gordeladze JO, Drevon CA. 2001. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res 16:1426-1433.
187. Reseland JE, Reppe S, Larsen AM, Berner HS, Reinholt FP, Gautvik KM, Slaby I, Lyngstadaas SP. 2006. The effect of enamel matrix derivative on gene expression in osteoblasts. Eur J Oral Sci 114 Suppl 1:205-211; discussion 254-206, 381-202.
188. Rizzo V, Sung A, Oh P, Schnitzer JE. 1998. Rapid mechanotransduction in situ at the luminal cell surface of vascular endothelium and its caveolae. J Biol Chem 273:26323-26329.
189. Robledo RF, Rajan L, Li X, Lufkin T. 2002. The dlx5 and dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev 16:1089-1101.
190. Robling AG, Bellido T, Turner CH. 2006a. Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact 6:354.
191. Robling AG, Castillo AB, Turner CH. 2006b. Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455-498.
192. Rosen H, Goetzl EJ. 2005. Sphingosine 1-phosphate and its receptors: An autocrine and paracrine network. Nat Rev Immunol 5:560-570.
193. Rubin CT, Lanyon LE. 1984. Dynamic strain similarity in vertebrates: An alternative to allometric limb bone scaling. J Theor Biol 107:321-327.
194. Rubin CT, McLeod KJ. 1994. Promotion of bony ingrowth by frequencyspecific, low-amplitude mechanical strain. Clin Orthop Relat Res: 165-174.
195. Rubin C, Xu G, Judex S. 2001. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely lowmagnitude mechanical stimuli. FASEB J 15:2225-2229.
196. Rubin C, Recker R, Cullen D, Ryaby J, McCabe J, McLeod K. 2004. Prevention of postmenopausal bone loss by low-magnitude, high-frequency mechanical stimuli: A clinical trial assessing compliance, efficacy, and safety. J Bone Miner Res 19:343-351.
197. Rubin J, Fan X, Biskobing DM, Taylor WR, Rubin CT. 1999. Osteoclastogenesis is repressed by mechanical strain in an in vitro model. J Orthop Res 17:639-645.
198. Rubin J, Murphy TC, Fan X, Goldschmidt M, Taylor WR. 2002. Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of rankl expression in bone stromal cells. J Bone Miner Res 17:1452-1460.
199. Rubin J, Murphy TC, Zhu L, Roy E, Nanes MS, Fan X. 2003. Mechanical strain differentially regulates endothelial nitric-oxide synthase and receptor activator of nuclear kappa b ligand expression via ERK1/2 MAPK. J Biol Chem 278:34018-34025.
200. Rubin J, Rubin C, Jacobs CR. 2006. Molecular pathways mediating mechanical signaling in bone. Gene 367:1-16.
201. Rubinacci A, Marenzana M, Cavani F, Colasante F, Villa I, Willnecker J, Moro GL, Spreafico LP, Ferretti M, Guidobono F, Marotti G. 2008. Ovariectomy sensitizes rat cortical bone to whole body vibration. Calcif Tissue Int 82:316-326.
202. Ryder KD, Duncan RL. 2001. Parathyroid hormone enhances fl uid shearinduced [ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive ca2+ channels. J Bone Miner Res 16:240-248.
203. Ryoo HM, Lee MH, Kim YJ. 2006. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366:51-57.
204. Ryu J, Kim HJ, Chang EJ, Huang H, Banno Y, Kim HH. 2006. Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclastosteoblast coupling. Embo J 25:5840-5851.
205. Schaller MD. 1996. The focal adhesion kinase. J Endocrinol 150:1-7.
206. Schlaepfer DD, Broome MA, Hunter T. 1997. Fibronectin-stimulated signaling from a focal adhesion kinase-c-src complex: Involvement of the grb2, p130cas, and nck adaptor proteins. Mol Cell Biol 17:1702-1713.
207. Schlaepfer DD, Jones KC, Hunter T. 1998. Multiple grb2-mediated integrinstimulated signaling pathways to erk2/mitogen-activated protein kinase: Summation of both c-src- and focal adhesion kinase-initiated tyrosine phosphorylation events. Mol Cell Biol 18:2571-2585.
208. Schlaepfer DD, Hauck CR, Sieg DJ. 1999. Signaling through focal adhesion kinase. Prog Biophys Mol Biol 71:435-478.
209. Schmidt K, Schinke T, Haberland M, Priemel M, Schilling AF, Mueldner C, Rueger JM, Sock E, Wegner M, Amling M. 2005. The high mobility group transcription factor sox8 is a negative regulator of osteoblast differentiation. J Cell Biol 168:899-910.
210. Sheedy FJ, O'Neill LA. 2008. Adding fuel to fire: MicroRNAs as a new class of mediators of infl ammation. Ann Rheum Dis 67 Suppl 3:iii50-iii55.
211. Shen L, Zhou S, Glowacki J. 2009. Effects of age and gender on Wnt gene expression in human bone marrow stromal cells. J Cell Biochem 106:337-343.
212. Shimoaka T, Kamekura S, Chikuda H, Hoshi K, Chung UI, Akune T, Maruyama Z, Komori T, Matsumoto M, Ogawa W, Terauchi Y, Kadowaki T, Nakamura K, Kawaguchi H. 2004. Impairment of bone healing by insulin receptor substrate-1 deficiency. J Biol Chem 279:15314-15322.
213. Shirakabe K, Terasawa K, Miyama K, Shibuya H, Nishida E. 2001. Regulation of the activity of the transcription factor runx2 by two homeobox proteins, msx2 and dlx5. Genes Cells 6:851-856.
214. Skerry TM. 2006. One mechanostat or many? Modifications of the sitespecific response of bone to mechanical loading by nature and nurture. J Musculoskelet Neuronal Interact 6:122-127.
215. Skerry TM. 2008. The response of bone to mechanical loading and disuse: Fundamental principles and infl uences on osteoblast/osteocyte homeostasis. Arch Biochem Biophys 473:117-123.
216. Smalt R, Mitchell FT, Howard RL, Chambers TJ. 1997. Induction of NO and prostaglandin e2 in osteoblasts by wall-shear stress but not mechanical strain. Am J Physiol 273:E751-E758.
217. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G. 2002. Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305-317.
218. Tare RS, Khan F, Tourniaire G, Morgan SM, Bradley M, Oreffo RO. 2009. A microarray approach to the identification of polyurethanes for the isolation of human skeletal progenitor cells and augmentation of skeletal cell growth. Biomaterials 30:1045-1055.
219. Toma CD, Ashkar S, Gray ML, Schaffer JL, Gerstenfeld LC. 1997. Signal transduction of mechanical stimuli is dependent on microfilament integrity: Identification of osteopontin as a mechanically induced gene in osteoblasts. J Bone Miner Res 12:1626-1636.
220. Tong AW, Nemunaitis J. 2008. Modulation of miRNA activity in human cancer: A new paradigm for cancer gene therapy? Cancer Gene Ther 15:341-355.
221. Torcasio A, van Lenthe GH, Van Oosterwyck H. 2008. The importance of loading frequency, rate and vibration for enhancing bone adaptation and implant osseointegration. Eur Cell Mater 16:56-68.
222. Tribioli C, Lufkin T. 1999. The murine bapx1 homeobox gene plays a critical role in embryonic development of the axial skeleton and spleen. Development 126:5699-5711.
223. Tu Q, Valverde P, Chen J. 2006. Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells. Biochem Biophys Res Commun 341:1257-1265.
224. Verschueren SM, Roelants M, Delecluse C, Swinnen S, Vanderschueren D, Boonen S. 2004. Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: A randomized controlled pilot study. J Bone Miner Res 19:352-359.
225. Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. 2004. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res 19:360-369.
226. Wazen RM, Moffatt P, Zalzal SF, Daniel NG, Westerman KA, Nanci A. 2006. Local gene transfer to calcified tissue cells using prolonged infusion of a lentiviral vector. Gene Ther 13:1595-1602.
227. Weinbaum S, Cowin SC, Zeng Y. 1994. A model for the excitation of osteocytes by mechanical loading-induced bone fl uid shear stresses. J Biomech 27:339-360.
228. Westendorf JJ. 2006. Transcriptional co-repressors of runx2. J Cell Biochem 98:54-64.
229. Westendorf JJ, Kahler RA, Schroeder TM. 2004. Wnt signaling in osteoblasts and bone diseases. Gene 341:19-39.
230. Weyts FA, Li YS, van Leeuwen J, Weinans H, Chien S. 2002. ERK activation and alpha v beta 3 integrin signaling through SHC recruitment in response to mechanical stimulation in human osteoblasts. J Cell Biochem 87:85-92.
231. Wiltink A, Nijweide PJ, Scheenen WJ, Ypey DL, Van Duijn B. 1995. Cell membrane stretch in osteoclasts triggers a self-reinforcing ca2+ entry pathway. Pfl ugers Arch 429:663-671.
232. Winslow MM, Pan M, Starbuck M, Gallo EM, Deng L, Karsenty G, Crabtree GR. 2006. Calcineurin/nfat signaling in osteoblasts regulates bone mass. Dev Cell 10:771-782.
233. Xiao G, Jiang D, Thomas P, Benson MD, Guan K, Karsenty G, Franceschi RT. 2000. MAPK pathways activate and phosphorylate the osteoblastspecific transcription factor, cbfa1. J Biol Chem 275:4453-4459.
234. Xiao G, Jiang D, Ge C, Zhao Z, Lai Y, Boules H, Phimphilai M, Yang X, Karsenty G, Franceschi RT. 2005. Cooperative interactions between activating transcription factor 4 and runx2/cbfa1 stimulate osteoblastspecific osteocalcin gene expression. J Biol Chem 280:30689-30696.
235. Xie L, Jacobson JM, Choi ES, Busa B, Donahue LR, Miller LM, Rubin CT, Judex S. 2006. Low-level mechanical vibrations can infl uence bone resorption and bone formation in the growing skeleton. Bone 39: 1059-1066.
236. Xie L, Rubin C, Judex S. 2008. Enhancement of the adolescent murine musculoskeletal system using low-level mechanical vibrations. J Appl Physiol 104:1056-1062.
237. Yamada Y, Boo JS, Ozawa R, Nagasaka T, Okazaki Y, Hata K, Ueda M. 2003. Bone regeneration following injection of mesenchymal stem cells and fibrin glue with a biodegradable scaffold. J Craniomaxillofac Surg 31:27-33.
238. Yan C, Takahashi M, Okuda M, Lee JD, Berk BC. 1999. Fluid shear stress stimulates big mitogen-activated protein kinase 1 (BMK1) activity in endothelial cells: Dependence on tyrosine kinases and intracellular calcium. J Biol Chem 274:143-150.
239. Yang X, Karsenty G. 2004. Atf4, the osteoblast accumulation of which is determined post-translationally, can induce osteoblast-specific gene expression in non-osteoblastic cells. J Biol Chem 279:47109-47114.
240. Yang CM, Chien CS, Yao CC, Hsiao LD, Huang YC, Wu CB. 2004a. Mechanical strain induces collagenase-3 (mmp-13) expression in mc3t3-e1 osteoblastic cells. J Biol Chem 279:22158-22165.
241. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, Hanauer A, Karsenty G. 2004b. Atf4 is a substrate of rsk2 and an essential regulator of osteoblast biology: Implication for Coffin-Lowry syndrome. Cell 117:387-398.
242. Yellowley CE, Li Z, Zhou Z, Jacobs CR, Donahue HJ. 2000. Functional gap junctions between osteocytic and osteoblastic cells. J Bone Miner Res 15:209-217.
243. Yin T, Li L. 2006. The stem cell niches in bone. J Clin Invest 116:1195-1201.
244. You J, Reilly GC, Zhen X, Yellowley CE, Chen Q, Donahue HJ, Jacobs CR. 2001. Osteopontin gene regulation by oscillatory fl uid fl ow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in mc3t3-e1 osteoblasts. J Biol Chem 276:13365-13371.
245. Yousfi M, Lasmoles F, El Ghouzzi V, Marie PJ. 2002. Twist haploinsufficiency in Saethre-Chotzen syndrome induces calvarial osteoblast apoptosis due to increased TNFalpha expression and caspase-2 activation. Hum Mol Genet 11:359-369.
246. Yuan J, Cui L, Zhang WJ, Liu W, Cao Y. 2007. Repair of canine mandibular bone defects with bone marrow stromal cells and porous beta-tricalcium phosphate. Biomaterials 28:1005-1013.
247. Zaman G, Pitsillides AA, Rawlinson SC, Suswillo RF, Mosley JR, Cheng MZ, Platts LA, Hukkanen M, Polak JM, Lanyon LE. 1999. Mechanical strain stimulates nitric oxide production by rapid activation of endothelial nitric oxide synthase in osteocytes. J Bone Miner Res 14:1123-1131.
248. Zeidan A, Broman J, Hellstrand P, Sward K. 2003. Cholesterol dependence of vascular ERK1/2 activation and growth in response to stretch: Role of endothelin-1. Arterioscler Thromb Vasc Biol 23:1528-1534.
249. Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harris S, Wiedemann LM, Mishina Y, Li L. 2003. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425:836-841.
250. Zhang YW, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K, Ito Y. 2000. A runx2/pebp2alpha a/cbfa1 mutation displaying impaired transactivation and smad interac tion in cleidocranial dysplasia. Proc Natl Acad Sci U S A 97:10549-10554.
251. Zhou G, Zheng Q, Engin F, Munivez E, Chen Y, Sebald E, Krakow D, Lee B. 2006. Dominance of sox9 function over runx2 during skeletogenesis. Proc Natl Acad Sci U S A 103:19004-19009.
252. Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS, Glowacki J. 2008. Age-related intrinsic changes in human bonemarrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell 7:335-343.
253. Zhou Y, Ferguson J, Chang JT, Kluger Y. 2007. Inter- and intra-combinatorial regulation by transcription factors and microRNAs. BMC Genomics 8:396.
254. Ziambaras K, Lecanda F, Steinberg TH, Civitelli R. 1998. Cyclic stretch enhances gap junctional communication between osteoblastic cells. J Bone Miner Res 13:218-228.