Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration

Birth Defects Research Part C - Embryo Today: Reviews

Volumn 99, Issue 3, 2013, Pages 170-191

  Dirckx, Naomi ^a   Van Hul, Matthias ^a   Maes, Christa ^a  

^a SKELETAL BIOLOGY AND ENGINEERING RESEARCH CENTER   (Belgium)

Author keywords

Angiogenesis; Bone formation; Bone repair; Chemotaxis; Osteoblast recruitment; Osteoprogenitor

Indexed keywords

BASIC FIBROBLAST GROWTH FACTOR RECEPTOR; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEIN 6; COMPLEMENT COMPONENT C5A; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 4; OSTEOBLAST STIMULATING FACTOR 1; OSTEOGENIC PROTEIN 1; PLATELET DERIVED GROWTH FACTOR AA; PLATELET DERIVED GROWTH FACTOR AB; PLATELET DERIVED GROWTH FACTOR BB; RANTES; SOMATOMEDIN B; SOMATOMEDIN C; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; VASCULOTROPIN A; VASCULOTROPIN C; VASCULOTROPIN E; VASCULOTROPIN RECEPTOR 1;

ANGIOGENESIS; BONE BLOOD FLOW; BONE DEVELOPMENT; BONE REGENERATION; BONE REMODELING; BONE TURNOVER; CELL DIFFERENTIATION; CELL LINEAGE; CELL MIGRATION; CHEMOTAXIS; COUPLING FACTOR; CROSS COUPLING REACTION; ENCHONDRAL OSSIFICATION; GENETICALLY ENGINEERED MOUSE STRAIN; HEMATOPOIETIC STEM CELL; HOMEOSTASIS; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NEOVASCULARIZATION (PATHOLOGY); NONHUMAN; OSSIFICATION; OSTEOBLAST; PERICHONDRIUM; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; VASCULARIZATION;

ANGIOGENESIS; BONE FORMATION; BONE REPAIR; CHEMOTAXIS; OSTEOBLAST RECRUITMENT; OSTEOPROGENITOR;

ANIMALS; BONE AND BONES; CARTILAGE; CELL DIFFERENTIATION; CELL LINEAGE; HOMEOSTASIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; MODELS, ANIMAL; OSTEOBLASTS; OSTEOGENESIS; REGENERATION; TISSUE ENGINEERING; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84884947186     PISSN: 1542975X     EISSN: 15429768     Source Type: Journal    
DOI: 10.1002/bdrc.21047     Document Type: Review

References (138)

1. Abdennagy B, Hott M, Marie PJ. 1992. Effects of platelet-derived growth factor on human and mouse osteoblastic cells isolated from the trabecular bone surface. Cell Biol Int Rep 16:235-247.
2. Akiyama H, Kim JE, Nakashima K, et al. 2005. Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc Natl Acad Sci USA 102:14665-14670.
3. Amarilio R, Viukov S, Sharir A, et al. 2007. Hif1alpha regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early chondrogenesis. Development 134:3917-3928.
4. Andersen TL, Sondergaard TE, Skorzynska KE, et al. 2009. A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol 174:239-247.
5. Annabi B, Lee YT, Turcotte S, et al. 2003. Hypoxia promotes murine bone-marrow-derived stromal cell migration and tube formation. Stem Cells 21:337-347.
6. Araldi E, Khatri R, Giaccia AJ, et al. 2011. Lack of HIF-2alpha in limb bud mesenchyme causes a modest and transient delay of endochondral bone development. Nat Med 17:25-26.
7. Augello A, Kurth TB, DeBari C. 2010. Mesenchymal stem cells: A perspective from in vitro cultures to in vivo migration and niches. Eur Cell Mater 20:121-133.
8. Baron R, Hesse E. 2012. Update on bone anabolics in osteoporosis treatment: Rationale, current status, and perspectives. J Clin Endocrinol Metab 97:311-325.
9. Beamer B, Hettrich C, Lane J. 2010. Vascular endothelial growth factor: An essential component of angiogenesis and fracture healing. HSS J 6:85-94.
10. Beck GR Jr, Zerler B, Moran E. 2001. Gene array analysis of osteoblast differentiation. Cell Growth Differ 12:61-83.
11. Bentovim L, Amarilio R, Zelzer E. 2012. HIF1alpha is a central regulator of collagen hydroxylation and secretion under hypoxia during bone development. Development 139:4473-4483.
12. Bonewald LF. 2011. The amazing osteocyte. J Bone Miner Res 26:229-238.
13. Bouletreau PJ, Warren SM, Spector JA, et al. 2002. Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: Implications for fracture healing. Plast Reconstr Surg 109:2384-2397.
14. Bueno EM, Glowacki J. 2009. Cell-free and cell-based approaches for bone regeneration. Nat Rev Rheumatol 5:685-697.
15. Burkhardt R, Kettner G, Bohm W, et al. 1987. Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: A comparative histomorphometric study. Bone 8:157-164.
16. Canalis E, Varghese S, Mccarthy TL, Centrella M. 1992. Role of platelet derived growth factor in bone cell function. Growth Regul 2:151-155.
17. Case N, Rubin J. 2010. Beta-catenin-A supporting role in the skeleton. J Cell Biochem 110:545-553.
18. Chen J, Long F. 2013. beta-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice. J Bone Miner Res 28:1160-1169.
19. Christensen JL, Wright DE, Wagers AJ, Weissman IL. 2004. Circulation and chemotaxis of fetal hematopoietic stem cells. PLoS Biol 2:E75.
20. Colciago A, Celotti F, Casati L, et al. 2009. In vitro effects of PDGF isoforms (AA, BB, AB and CC) on migration and proliferation of SaOS-2 osteoblasts and on migration of human osteoblasts. Int J Biomed Sci 5:380-389.
21. Colnot C. 2009. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration. J Bone Miner Res 24:274-282.
22. Colnot C, Lu C, Hu D, Helms JA. 2004. Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol 269:55-69.
23. Colnot C, Thompson Z, Miclau T, et al. 2003. Altered fracture repair in the absence of MMP9. Development 130:4123-4133.
24. Crisan M, Yap S, Casteilla L, et al. 2008. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301-313.
25. Dai J, Rabie AB. 2007. VEGF: An essential mediator of both angiogenesis and endochondral ossification. J Dent Res 86:937-950.
26. Elefteriou F, Yang X. 2011. Genetic mouse models for bone studies-Strengths and limitations. Bone 49:1242-1254.
27. Eshkar-Oren I, Viukov SV, Salameh S, et al. 2009. The forming limb skeleton serves as a signaling center for limb vasculature patterning via regulation of Vegf. Development 136:1263-1272.
28. Felsenberg D, Silman AJ, Lunt M, et al. 2002. Incidence of vertebral fracture in Europe: Results from the European prospective osteoporosis study (EPOS). J Bone Miner Res 17:716-724.
29. Ferguson CM, Miclau T, Hu D, et al. 1998. Common molecular pathways in skeletal morphogenesis and repair. Ann N Y Acad Sci 857:33-42.
30. Fiedler J, Etzel N, Brenner RE. 2004. To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem 93:990-998.
31. Fiedler J, Leucht F, Waltenberger J, et al. 2005. VEGF-A and PlGF-1 stimulate chemotactic migration of human mesenchymal progenitor cells. Biochem Biophys Res Commun 334:561-568.
32. Fiedler J, Roderer G, Gunther KP, Brenner RE. 2002. BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem 87:305-312.
33. Franceschi RT. 2005. Biological approaches to bone regeneration by gene therapy. J Dent Res 84:1093-1103.
34. Galotto M, Campanile G, Robino G, et al. 1994. Hypertrophic chondrocytes undergo further differentiation to osteoblast-like cells and participate in the initial bone formation in developing chick embryo. J Bone Miner Res 9:1239-1249.
35. Gamell C, Osses N, Bartrons R, et al. 2008. BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity. J Cell Sci 121:3960-3970.
36. Gentili C, Bianco P, Neri M, et al. 1993. Cell proliferation, extracellular matrix mineralization, and ovotransferrin transient expression during in vitro differentiation of chick hypertrophic chondrocytes into osteoblast-like cells. J Cell Biol 122:703-712.
37. Gerber HP, Vu TH, Ryan AM, et al. 1999. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623-628.
38. Gerstenfeld LC, Cullinane DM, Barnes GL, et al. 2003. Fracture healing as a post-natal developmental process: Molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88:873-884.
39. Godwin SL, Soltoff SP. 1997. Extracellular calcium and platelet-derived growth factor promote receptor-mediated chemotaxis in osteoblasts through different signaling pathways. J Biol Chem 272:11307-11312.
40. Gomez-Barrena E, Rosset P, Muller I, et al. 2011. Bone regeneration: Stem cell therapies and clinical studies in orthopaedics and traumatology. J Cell Mol Med 15:1266-1286.
41. Grellier M, Bordenave L, Amedee J. 2009. Cell-to-cell communication between osteogenic and endothelial lineages: Implications for tissue engineering. Trends Biotechnol 27:562-571.
42. Hah YS, Jun JS, Lee SG, et al. 2011. Vascular endothelial growth factor stimulates osteoblastic differentiation of cultured human periosteal-derived cells expressing vascular endothelial growth factor receptors. Mol Biol Rep 38:1443-1450.
43. Hartmann C. 2009. Transcriptional networks controlling skeletal development. Curr Opin Genet Dev 19:437-443.
44. Haupt LM, Murali S, Mun FK, et al. 2009. The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis. J Cell Physiol 220:780-791.
45. Helms JA, Schneider RA. 2003. Cranial skeletal biology. Nature 423:326-331.
46. Hengartner NE, Fiedler J, Ignatius A, Brenner RE. 2013. IL-1beta inhibits human osteoblast migration. Mol Med 19:36-42.
47. Henriksen K, Neutzsky-Wulff AV, Bonewald LF, Karsdal MA. 2009. Local communication on and within bone controls bone remodeling. Bone 44:1026-1033.
48. Hill TP, Spater D, Taketo MM, et al. 2005. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727-738.
49. Hilton MJ, Tu X, Long F. 2007. Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage. Dev Biol 308:93-105.
50. Hughes A, Kleine-Albers J, Helfrich MH, et al. 2012. A class III semaphorin (Sema3e) inhibits mouse osteoblast migration and decreases osteoclast formation in vitro. Calcif Tissue Int 90:151-162.
51. Hughes FJ, Aubin JE, Heersche JN. 1992. Differential chemotactic responses of different populations of fetal rat calvaria cells to platelet-derived growth factor and transforming growth factor beta. Bone Miner 19:63-74.
52. Ichida M, Yui Y, Yoshioka K, et al. 2011. Changes in cell migration of mesenchymal cells during osteogenic differentiation. FEBS Lett 585:4018-4024.
53. Jacobsen KA, AlAql ZS, Wan C, et al. 2008. Bone formation during distraction osteogenesis is dependent on both VEGFR1 and VEGFR2 signaling. J Bone Miner Res 23:596-609.
54. Kalajzic Z, Li H, Wang LP, et al. 2008. Use of an alpha-smooth muscle actin GFP reporter to identify an osteoprogenitor population. Bone 43:501-510.
55. Keramaris NC, Calori GM, Nikolaou VS, et al. 2008. Fracture vascularity and bone healing: A systematic review of the role of VEGF. Injury 39 (Suppl 2):S45-S57.
56. Khosla S, Westendorf JJ, Modder UI. 2010. Concise review: Insights from normal bone remodeling and stem cell-based therapies for bone repair. Stem Cells 28:2124-2128.
57. Komori T. 2010. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res 339:189-195.
58. Kronenberg HM. 2003. Developmental regulation of the growth plate. Nature 423:332-336.
59. Kronenberg HM. 2007. The role of the perichondrium in fetal bone development. Ann N Y Acad Sci 1116:59-64.
60. Kulawig R, Kruger JP, Klein O, et al. 2013. Identification of fibronectin as a major factor in human serum to recruit subchondral mesenchymal progenitor cells. Int J Biochem Cell Biol 45:1410-1418.
61. Kumar S, Ponnazhagan S. 2012. Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect. Bone 50:1012-1018.
62. Kumar S, Wan C, Ramaswamy G, et al. 2010. Mesenchymal stem cells expressing osteogenic and angiogenic factors synergistically enhance bone formation in a mouse model of segmental bone defect. Mol Ther 18:1026-1034.
63. Lafage-Proust MH, Prisby R, Roche B, Vico L. 2010. Bone vascularization and remodeling. Joint Bone Spine 77:521-524.
64. Lee DH, Park BJ, Lee MS, et al. 2006. Chemotactic migration of human mesenchymal stem cells and MC3T3-E1 osteoblast-like cells induced by COS-7 cell line expressing rhBMP-7. Tissue Eng 12:1577-1586.
65. Li G, Cui Y, Mcilmurray L, et al. 2005. rhBMP-2, rhVEGF(165), rhPTN and thrombin-related peptide, TP508 induce chemotaxis of human osteoblasts and microvascular endothelial cells. J Orthop Res 23:680-685.
66. Lienau J, Schmidt-Bleek K, Peters A, et al. 2009. Differential regulation of blood vessel formation between standard and delayed bone healing. J Orthop Res 27:1133-1140.
67. Lind M, Deleuran B, Thestrup-Pedersen K, et al. 1995a. Chemotaxis of human osteoblasts. Effects of osteotropic growth factors. APMIS 103:140-146.
68. Lind M, Deleuran B, Yssel H, et al. 1995b. IL-4 and IL-13, but not IL-10, are chemotactic factors for human osteoblasts. Cytokine 7:78-82.
69. Lind M, Eriksen EF, Bunger C. 1996. Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. Bone 18:53-57.
70. Liu Y, Berendsen AD, Jia S, et al. 2012. Intracellular VEGF regulates the balance between osteoblast and adipocyte differentiation. J Clin Invest 122:3101-3113.
71. Long F. 2012. Building strong bones: Molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 13:27-38.
72. Maes C. 2013. Role and regulation of vascularization processes in endochondral bones. Calcif Tissue Int 92:307-323.
73. Maes C, Araldi E, Haigh K, et al. 2012a. VEGF-independent cell-autonomous functions of HIF-1alpha regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival. J Bone Miner Res 27:596-609.
74. Maes C, Carmeliet G, Schipani E. 2012b. Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol 8:358-366.
75. Maes C, Carmeliet P, Moermans K, et al. 2002. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech Dev 111:61-73.
76. Maes C, Coenegrachts L, Stockmans I, et al. 2006. Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair. J Clin Invest 116:1230-1242.
77. Maes C, Goossens S, Bartunkova S, et al. 2010a. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J 29:424-441.
78. Maes C, Kobayashi T, Selig MK, et al. 2010b. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 19:329-344.
79. Maes C, Stockmans I, Moermans K, et al. 2004. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest 113:188-199.
80. Mayer H, Bertram H, Lindenmaier W, et al. 2005. Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: Autocrine and paracrine role on osteoblastic and endothelial differentiation 1. J Cell Biochem 95:827-839.
81. Mayr-Wohlfart U, Waltenberger J, Hausser H, et al. 2002. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone 30:472-477.
82. Mehrotra M, Krane SM, Walters K, Pilbeam C. 2004. Differential regulation of platelet-derived growth factor stimulated migration and proliferation in osteoblastic cells. J Cell Biochem 93:741-752.
83. Mendez-Ferrer S, Michurina TV, Ferraro F, et al. 2010. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829-834.
84. Midy VPlouet J. 1994. Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts. Biochem Biophys Res Commun 199:380-386.
85. Nakasaki M, Yoshioka K, Miyamoto Y, et al. 2008. IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts. Bone 43:869-879.
86. Nakashima K, Zhou X, Kunkel G, et al. 2002. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17-29.
87. Nakashima T, Hayashi M, Fukunaga T, et al. 2011. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med 17:1231-1234.
88. Negishi-Koga T, Shinohara M, Komatsu N, et al. 2011. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat Med 17:1473-1480.
89. Otsuru S, Tamai K, Yamazaki T, et al. 2008. Circulating bone marrow-derived osteoblast progenitor cells are recruited to the bone-forming site by the CXCR4/stromal cell-derived factor-1 pathway. Stem Cells 26:223-234.
90. Panagakos FS. 1993. Insulin-like growth factors-I and -II stimulate chemotaxis of osteoblasts isolated from fetal rat calvaria. Biochimie 75:991-994.
91. Panagakos FS. 1994. Transforming growth factor-Alpha stimulates chemotaxis of osteoblasts and osteoblast-like cells in vitro. Biochem Mol Biol Int 33:643-650.
92. Peng H, Wright V, Usas A, et al. 2002. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest 110:751-759.
93. Pfander D, Kobayashi T, Knight M, et al. 2004. Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development. Development 131:2497-2508.
94. Pignolo RJ, Kassem M. 2011. Circulating osteogenic cells: implications for injury, repair, and regeneration. J Bone Miner Res 26:1685-1693.
95. Provot S, Zinyk D, Gunes Y, et al. 2007. Hif-1alpha regulates differentiation of limb bud mesenchyme and joint development. J Cell Biol 177:451-464.
96. Rachner TD, Khosla S, Hofbauer LC. 2011. Osteoporosis: Now and the future. Lancet 377:1276-1287.
97. Raheja LF, Genetos DC, Wong A, Yellowley CE. 2011. Hypoxic regulation of mesenchymal stem cell migration: The role of RhoA and HIF-1alpha. Cell Biol Int 35:981-989.
98. Raheja LF, Genetos DC, Yellowley CE. 2008. Hypoxic osteocytes recruit human MSCs through an OPN/CD44-mediated pathway. Biochem Biophys Res Commun 366:1061-1066.
99. Rankin EB, Wu C, Khatri R, et al. 2012. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell 149:63-74.
100. Riddle RC, Khatri R, Schipani EClemens TL. 2009. Role of hypoxia-inducible factor-1alpha in angiogenic-osteogenic coupling. J Mol Med 87:583-590.
101. Roach HI, Erenpreisa J. 1996. The phenotypic switch from chondrocytes to bone-forming cells involves asymmetric cell division and apoptosis. Connect Tissue Res 35:85-91.
102. Rodda SJ, Mcmahon AP. 2006. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133:3231-3244.
103. Sacchetti B, Funari A, Michienzi S, et al. 2007. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324-336.
104. Saito T, Fukai A, Mabuchi A, et al. 2010. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16:678-686.
105. Saller MM, Prall WC, Docheva D, et al. 2012. Increased stemness and migration of human mesenchymal stem cells in hypoxia is associated with altered integrin expression. Biochem Biophys Res Commun 423:379-385.
106. Sanchez-Fernandez MA, Gallois A, Riedl T, et al. 2008. Osteoclasts control osteoblast chemotaxis via PDGF-BB/PDGF receptor beta signaling. PLoS One 3:e3537.
107. Schindeler A, Mcdonald MM, Bokko P, Little DG. 2008. Bone remodeling during fracture repair: The cellular picture. Semin Cell Dev Biol 19:459-466.
108. Schipani E, Maes C, Carmeliet G, Semenza GL. 2009. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J Bone Miner Res 24:1347-1353.
109. Schipani E, Ryan HE, Didrickson S, et al. 2001. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev 15:2865-2876.
110. Semenza GL. 2012. Hypoxia-inducible factors in physiology and medicine. Cell 148:399-408.
111. Shapiro IM, Adams CS, Freeman T, Srinivas V. 2005. Fate of the hypertrophic chondrocyte: Microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate. Birth Defects Res C Embryo Today 75:330-339.
112. Shen X, Wan C, Ramaswamy G, et al. 2009. Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J Orthop Surg 27:1298-1305.
113. Shomento SH, Wan C, Cao X, et al. 2010. Hypoxia-inducible factors 1alpha and 2alpha exert both distinct and overlapping functions in long bone development. J Cell Biochem 109:196-204.
114. Shum L, Coleman CM, Hatakeyama Y, Tuan RS. 2003. Morphogenesis and dysmorphogenesis of the appendicular skeleton. Birth Defects Res C Embryo Today 69:102-122.
115. Sims NA, Gooi JH. 2008. Bone remodeling: Multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol 19:444-451.
116. Song L, Liu M, Ono N, et al. 2012. Loss of wnt/beta-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes. J Bone Miner Res 27:2344-2358.
117. Street J, Bao M, Deguzman L, et al. 2002. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci USA 99:9656-9661.
118. Ström O, Borgström F, Kanis JA, Compston J, Cooper C, McCloskey EV, Jönsson B. 2011. Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA).
119. Sugiyama T, Kohara H, Noda M, Nagasawa T. 2006. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25:977-988.
120. Tabin C, Wolpert L. 2007. Rethinking the proximodistal axis of the vertebrate limb in the molecular era. Genes Dev 21:1433-1442.
121. Taguchi K, Ogawa R, Migita M, et al. 2005. The role of bone marrow-derived cells in bone fracture repair in a green fluorescent protein chimeric mouse model. Biochem Biophys Res Commun 331:31-36.
122. Tang W, Yang F, Li Y, et al. 2012. Transcriptional regulation of vascular endothelial growth factor (VEGF) by osteoblast-specific transcription factor Osterix (Osx) in osteoblasts. J Biol Chem 287:1671-1678.
123. Tang Y, Wu X, Lei W, et al. 2009. TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 15:757-765.
124. Tare RS, Babister JC, Kanczler J, Oreffo RO. 2008. Skeletal stem cells: Phenotype, biology and environmental niches informing tissue regeneration. Mol Cell Endo 288:11-21.
125. Towers M, Wolpert L, Tickle C. 2012. Gradients of signalling in the developing limb. Curr Opin Cell Biol 24:181-187.
126. Trueta J, Morgan JD. 1960. The vascular contribution to osteogenesis. I. Studies by the injection method. J Bone Joint Surg Br 42-B:97-109.
127. Tsuji K, Bandyopadhyay A, Harfe BD, et al. 2006. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet 38:1424-1429.
128. Tsukamoto T, Matsui T, Fukase M, Fujita T. 1991. Platelet-derived growth factor B chain homodimer enhances chemotaxis and DNA synthesis in normal osteoblast-like cells (MC3T3-E1). Biochem Biophys Res Commun 175:745-751.
129. Vertelov G, Kharazi L, Muralidhar MG, et al. 2013. High targeted migration of human mesenchymal stem cells grown in hypoxia is associated with enhanced activation of RhoA. Stem Cell Res Therapy 4:5.
130. Wan C, Gilbert SR, Wang Y, et al. 2008. Activation of the hypoxia-inducible factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci USA 105:686-691.
131. Wan C, Shao J, Gilbert SR, et al. 2010. Role of HIF-1alpha in skeletal development. Ann N Y Acad Sci 1192:322-326.
132. Wang Y, Wan C, Deng L, et al. 2007. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 117:1616-1626.
133. Weiss HE, Roberts SJ, Schrooten J, Luyten FP. 2012. A semi-autonomous model of endochondral ossification for developmental tissue engineering. Tissue Eng A 18:1334-1343.
134. Wildemann B, Burkhardt N, Luebberstedt M, et al. 2007. Proliferating and differentiating effects of three different growth factors on pluripotent mesenchymal cells and osteoblast like cells. J Orthop Surg Res 2:27.
135. Yang X, Tare RS, Partridge KA, et al. 2003. Induction of human osteoprogenitor chemotaxis, proliferation, differentiation, and bone formation by osteoblast stimulating factor-1/pleiotrophin: Osteoconductive biomimetic scaffolds for tissue engineering. J Bone Miner Res 18:47-57.
136. Yano S, Mentaverri R, Kanuparthi D, et al. 2005. Functional expression of beta-chemokine receptors in osteoblasts: Role of regulated upon activation, normal T cell expressed and secreted (RANTES) in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts. Endocrinology 146:2324-2335.
137. Yla-Herttuala S, Rissanen TT, Vajanto I, Hartikainen J. 2007. Vascular endothelial growth factors: Biology and current status of clinical applications in cardiovascular medicine. J Am Coll Cardiol 49:1015-1026.
138. Zelzer E, Mamluk R, Ferrara N, et al. 2004. VEGFA is necessary for chondrocyte survival during bone development. Development 131:2161-2171.