Functional impairment of bone formation in the pathogenesis of osteoporosis: The bone marrow regenerative competence

Current Osteoporosis Reports

Volumn 11, Issue 2, 2013, Pages 117-125

  Bidwell, Joseph P ^a   Alvarez, Marta B ^a   Hood Jr , Mark ^a   Childress, Paul ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Aging; Mesenchymal stem cells; Nmp4; Osteoblasts; Osteoprogenitors; Postmenopause

Indexed keywords

AGED; AGING; ARTICLE; BONE MARROW; BONE MATRIX; BONE METABOLISM; BONE REGENERATION; BONE REMODELING; CD8+ T LYMPHOCYTE; FUNCTIONAL DISEASE; HUMAN; MENOPAUSE; MESENCHYMAL STEM CELL; MICROENVIRONMENT; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOPOROSIS; PHENOTYPE; POPULATION DYNAMICS; POSTMENOPAUSE; STROMA CELL;

AGING; BONE MARROW CELLS; BONE REGENERATION; CELL DIFFERENTIATION; CELL PROLIFERATION; HUMANS; OSTEOBLASTS; OSTEOGENESIS; OSTEOPOROSIS;

EID: 84879094193     PISSN: 15441873     EISSN: 15442241     Source Type: Journal    
DOI: 10.1007/s11914-013-0139-2     Document Type: Article

References (90)

1. Manolagas SC, Parfitt AM. For whom the bell tolls: distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases. Bone. 2012. doi: 10.1016/j.bone.2012.09.017.
2. Hudec SM, Camacho PM. Secondary causes of osteoporosis. Endocr Pract. 2012;27:1-31.
3. Armas LA, Recker RR. Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am. 2012;41:475-86.
4. • Khosla S, Melton 3rd LJ, Riggs BL. The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed? J Bone Miner Res. 2011;26:441-51. This is an excellent comprehensive and cogent review on the pathogenesis of osteoporosis.
5. Pietschmann P, Rauner M, Sipos W, Kerschan-Schindl K. Osteoporosis: an age-related and gender-specific disease-a mini-review. Gerontology. 2009;55:3-12.
6. Duque G, Troen BR. Understanding the mechanisms of senile osteoporosis: new facts for a major geriatric syndrome. J Am Geriatr Soc. 2008;56:935-41.
7. Schuiling KD, Robinia K, Nye R. Osteoporosis update. J Midwifery Womens Health. 2011;56:615-27.
8. Mackiewicz Z, Niklińska WE, Kowalewska J, Chyczewski L. Bone as a source of organism vitality and regeneration. Folia Histochem Cytobiol. 2011;49:558-69.
9. Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res. 2005;20:177-84.
10. Eriksen EF. Cellular mechanisms of bone remodeling. Rev Endocr Metab Disord. 2010;11:219-27.
11. Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008. doi: 10.2215/CJN.04151206.
12. Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95:1555-65.
13. Beard MK. Bisphosphonate therapy for osteoporosis: combining optimal fracture risk reduction with patient preference. Curr Med Res Opin. 2012;28:141-7.
14. Rizzoli R, Akesson K, Bouxsein M, Kanis JA, Napoli N, Papapoulos S, et al. Subtrochanteric fractures after long-term treatment with bisphosphonates: a European society on clinical and economic aspects of osteoporosis and osteoarthritis, and international osteoporosis foundation working group report. Osteoporos Int. 2011;22:373-90.
15. Zhang J, Saag KG, Curtis JR. Long-term safety concerns of antiresorptive therapy. Rheum Dis Clin North Am. 2011;37:387-400.
16. Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011;305:783-9.
17. Stroup J, Kane MP, Abu-Baker AM. Teriparatide in the treatment of osteoporosis. Am J Health Syst Pharm. 2008;65:532-9.
18. Kraenzlin ME, Meier C. Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol. 2011;7:647-56.
19. Aslan D, Andersen MD, Gede LB, de Franca TK, Jørgensen SR, Schwarz P, et al. Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. Scand J Clin Lab Invest. 2012;72:14-22.
20. Jilka RL. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone. 2007;40:1434-46.
21. • Cusano NE, Bilezikian JP. Combination antiresorptive and osteoanabolic therapy for osteoporosis: we are not there yet. Curr Med Res Opin. 2011;27:1705-7. This is an instructive summary on the current progress and problems with PTH combination therapy.
22. Cusano NE, Bilezikian JP. Teriparatide: variations on the theme of a 2-year therapeutic course. IBMS BoneKey. 2010;7:84-7.
23. Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med. 2005;353:566-75.
24. Bilezikian JP. Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window. Curr Osteoporos Rep. 2008;6:24-30.
25. Koh AJ, Novince CM, Li X, Wang T, Taichman RS, McCauley LK. An irradiation-altered bone marrow microenvironment impacts anabolic actions of PTH. Endocrinology. 2011;152:4525-36.
26. Ohishi M, Schipani E. PTH and stem cells. J Endocrinol Investig. 2011;34:552-6.
27. •• Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG, Simmons PJ, et al. The meaning, the sense, and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med. 2013;19:35-42. This article is must reading for all in the bone field. It clearly and concisely describes the current understanding of the MSC phenotype and functional activity of these cells. It nicely distinguishes these cells from BMSCs.
28. •• Nombela-Arrieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol. 2011;12:126-31. This article should be read as a companion article to Bianco et al. 2013.
29. •• Park D, Spencer JA, Koh BI, Kobayashi T, Fujisaki J, Clemens TL, et al. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell. 2012;10:259-72. This is an elegant study demonstrating the existence of an Mx1+ subpopulation of nestin + cells that mediate bone-fracture repair.
30. • Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131:324-36. Earlier groundbreaking work by Bianco and colleagues in the description of CD146+ MSCs.
31. •• Bedi B, Li JY, Tawfeek H, Baek KH, Adams J, Vangara SS, et al. Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH. Proc Natl Acad Sci U S A. 2012;109:E725-33. Latest elegant work from Pacifici and colleagues on T cell involvement in PTH anabolic response.
32. • Terauchi M, Li JY, Bedi B, Baek KH, Tawfeek H, Galley S, et al. T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling. Cell Metab. 2009;10:229-40. Initial study showing CD8+ T cell involvement in PTH-induced anabolic bone formation.
33. Sinha KM, Zhou X. Genetic and molecular control of Osterix in skeletal formation. J Cell Biochem. 2012. doi: 10.1002/jcb.24439. Epub ahead of print.
34. Zhou X, Zhang Z, Feng JQ, Dusevich VM, Sinha K, Zhang H, et al. Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice. Proc Natl Acad Sci U S A. 2010;107:12919-24.
35. Nishio Y, Dong Y, Paris M, O'Keefe RJ, Schwarz EM, Drissi H. Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. Gene. 2006;372:62-70.
36. Zhou S, Geng S, Glowacki J. Histone deacetylation mediates the rejuvenation of osteoblastogenesis by the combination of 25(OH)D(3) and parathyroid hormone in MSCs from elders. J Steroid Biochem Mol Biol. 2012. doi: 10.1016/j.jsbmb.2012;.09.002.
37. Zhou S, Bueno EM, Kim SW, Amato I, Shen L, Hahne J, et al. Effects of age on parathyroid hormone signaling in human marrow stromal cells. Aging Cell. 2011;10:780-8.
38. Geng S, Zhou S, Glowacki J. Age-related decline in osteoblastogenesis and 1α-hydroxylase/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone. Aging Cell. 2011;10:962-71.
39. Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS, et al. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell. 2008;7:335-43.
40. Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M. Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. J Bone Miner Res. 2001;16:1120-9.
41. Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone. 2003;33:919-26.
42. Kassem M, Marie PJ. Senescence-associated intrinsic mechanisms of osteoblast dysfunctions. Aging Cell. 2011;10:191-7.
43. Sadie-Van Gijsen H, Crowther NJ, Hough FS, Ferris WF. The inter-relationship between bone and fat: from cellular see-saw to endocrine reciprocity. Cell Mol Life Sci. 2012. doi: 10.1007/s00018-012-1211-2.
44. Xing L, Boyce BF. Regulation of apoptosis in osteoclasts and osteoblastic cells. Biochem Biophys Res Commun. 2005;328:709-20.
45. Pacifici R. The immune system and bone. Arch Biochem Biophys. 2010;503:41-53.
46. Graham LS, Parhami F, Tintut Y, Kitchen CM, Demer LL, Effros RB. Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss. Clin Immunol. 2009;133:265-75.
47. Chou JP, Effros RB.T cell replicative senescence in human aging. Curr Pharm Des. 2012. PMID: 23061726.
48. Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, et al. The immune system in extreme longevity. Exp Gerontol. 2008;43:61-5.
49. Aubert G, Baerlocher GM, Vulto I, Poon SS, Lansdorp PM. Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes. PLoS Genet. 2012;8(5):e1002696. doi: 10.1371/journal.pgen. 1002696.
50. Tümpel S, Rudolph KL. The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems. Ann N Y Acad Sci. 2012;1266:28-39.
51. Lee HW, Blasco MA, Gottlieb GJ, Horner 2nd JW, Greider CW, DePinho RA. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392:569-74.
52. Singh L, Brennan TA, Kim JH, Egan KP, McMillan EA, Chen Q, et al. Long-term functional engraftment of mesenchymal progenitor cells in a mouse model of accelerated aging. Stem Cells. 2012. doi: 10.1002/stem.1294. Epub ahead of print.
53. Wang H, Chen Q, Lee SH, Choi Y, Johnson FB, Pignolo RJ. Impairment of osteoblast differentiation due to proliferation-independent telomere dysfunction in mouse models of accelerated aging. Aging Cell. 2012;11:704-13.
54. Pignolo RJ, Suda RK, McMillan EA, Shen J, Lee SH, Choi Y, et al. Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell. 2008;7:23-31.
55. Mendez-Bermudez A, Hidalgo-Bravo A, Cotton VE, Gravani A, Jeyapalan JN, Royle NJ. The roles of WRN and BLM RECQ helicases in the alternative lengthening of telomeres. Nucleic Acids Res. 2012;40:10809-20.
56. Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD. The Werner syndrome protein binds replication fork and holiday junction DNAs as an oligomer. J Biol Chem. 2008;283:24478-83.
57. Lu W, Zhang Y, Liu D, Songyang Z, Wan M. Telomeres-structure, function, and regulation. Exp Cell Res. 2013;319:133-41.
58. Lengner CJ, Steinman HA, Gagnon J, Smith TW, Henderson JE, Kream BE, et al. Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling. J Cell Biol. 2006;172:909-21.
59. •• Ye L, Fan Z, Yu B, Chang J, Al Hezaimi K, Zhou X, et al. Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs. Cell Stem Cell. 2012;11:50-61. Uses both mouse models and human bone marrow cells to convincingly show the key roles of KDM4B and KDM6B in driving osteoblastogenesis and their attenuated expression in aging and postmenopausal experimental preparations.
60. Teven CM, Liu X, Hu N, Tang N, Kim SH, Huang E, et al. Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation. Stem Cells Int. 2011;201371. doi: 10.4061/2011;/201371.
61. Stein GS, van Wijnen AJ, Imbalzano AN, Montecino M, Zaidi SK, Lian JB, et al. Architectural genetic and epigenetic control of regulatory networks: compartmentalizing machinery for transcription and chromatin remodeling in nuclear microenvironments. Crit Rev Eukaryot Gene Expr. 2010;20:149-55.
62. Ramírez J, Lukin K, Hagman J. From hematopoietic progenitors to B cells: mechanisms of lineage restriction and commitment. Curr Opin Immunol. 2010;22:177-84.
63. Napolitano MA, Cipollaro M, Cascino A, Melone MA, Giordano A, Galderisi U. Brg1 chromatin remodeling factor is involved in cell growth arrest, apoptosis and senescence of rat mesenchymal stem cells. J Cell Sci. 2007;120:2904-11.
64. • McGee-Lawrence ME, Bradley EW, Dudakovic A, Carlson SW, Ryan ZC, Kumar R, et al. Histone deacetylase 3 is required for maintenance of bone mass during aging. Bone. 2013;52:296-307. This is an elegant study showing Hdac3 role in supporting the anabolic competence of bone during aging.
65. Hesse E, Saito H, Kiviranta R, Correa D, Yamana K, Neff L, et al. Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity. J Cell Biol. 2010;191:1271-83.
66. Schroeder TM, Kahler RA, Li X, Westendorf JJ. Histone deacetylase 3 interacts with Runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation. J Biol Chem. 2004;279:41998-2007.
67. Diderich KE, Nicolaije C, Priemel M, Waarsing JH, Day JS, Brandt RM, et al. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice. Age. 2012;34:845-61.
68. Wakeling EL, Cruwys M, Suri M, Brady AF, Aylett SE, Hall C. Central osteosclerosis with trichothiodystrophy. Pediatr Radiol. 2004;34:541-6.
69. • Benisch P, Schilling T, Klein-Hitpass L, Frey SP, Seefried L, Raaijmakers N, et al. The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors. PLoS One. 2012;7:e45142. Interesting preliminary study demonstrating specific differences in BMSCs in young, old, and osteoporotic bone marrow samples.
70. Baldessari D, Badaloni A, Longhi R, Zappavigna V, Consalez GG. MAB21L2, a vertebrate member of the Male-abnormal 21 family, modulates BMP signaling and interacts with SMAD1. BMC Cell Biol. 2004;5:48.
71. Martin TJ, Sims NA, Ng KW. Regulatory pathways revealing new approaches to the development of anabolic drugs for osteoporosis. Osteoporos Int. 2008;19:1125-38.
72. Fu L, Patel MS, Karsenty G. The circadian modulation of leptin-controlled bone formation. Prog Brain Res. 2006;153:177-88.
73. Lowrey PL, Takahashi JS. Genetics of circadian rhythms in mammalian model organisms. Adv Genet. 2011;74:175-230.
74. Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP. Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev. 2006;20:1868-73.
75. • Chen Y, Xu X, Tan Z, Ye C, Zhao Q, Chen Y. Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential. Arch Med Sci. 2012;8:30-8. First study to relate circadian gene programs in bone with aging of BMSCs.
76. Kim KM, Park SJ, Jung SH, Kim EJ, Jogeswar G, Ajita J, et al. miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1. J Bone Miner Res. 2012;27:1669-79.
77. •• Yang N, Wang G, Hu C, Shi Y, Liao L, Shi S, et al. TNF-α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency-induced osteoporosis. J Bone Miner Res. 2012. doi: 10.1002/jbmr.1798 [Epub ahead of print]. Elegant and thorough study demonstrating attenuation of miR-21 function in maintaining anabolic phenotype in MSC/BMSCs during aging/osteoporosis.
78. Genetos DC, Zhou Z, Li Z, Donahue HJ. Age-related changes in gap junctional intercellular communication in osteoblastic cells. J Orthop Res. 2012;30:1979-84.
79. Donahue HJ, Zhou Z, Li Z, McCauley LK. Age-related decreases in stimulatory G protein-coupled adenylate cyclase activity in osteoblastic cells. Am J Physiol. 1997;273:E776-81.
80. • Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31:266-300. Excellent alternate frame of reference in considering the role of oxidative stress in the etiology of osteoporosis.
81. •• Xian L, Wu X, Pang L, Lou M, Rosen CJ, Qiu T, et al. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med. 2012;18:1095-101. Thorough and convincing study on the role of matrix-associated IGF-1 in supporting the anabolic competence of the bone marrow.
82. Sun Y, Li W, Lu Z, Chen R, Ling J, Ran Q, et al. Rescuing replication and osteogenesis of aged mesenchymal stem cells by exposure to a young extracellular matrix. FASEB J. 2011;25:1474-85.
83. He Y, Childress P, Hood Jr M, Alvarez M, Kacena MA, Hanlon M, et al. Nmp4/CIZ suppresses the parathyroid hormone anabolic window by restricting mesenchymal stem cell and osteoprogenitor frequency. Stem Cells Dev. 2013;22:492-500.
84. Childress P, Philip BK, Robling AG, Bruzzaniti A, Kacena MA, Bivi N, et al. Nmp4/CIZ suppresses the response of bone to anabolic parathyroid hormone by regulating both osteoblasts and osteoclasts. Calcif Tissue Int. 2011;89:74-89.
85. Robling AG, Childress P, Yu J, Cotte J, Heller A, Philip BK, et al. Nmp4/CIZ suppresses parathyroid hormone-induced increases in trabecular bone. J Cell Physiol. 2009;219:734-43.
86. Morinobu M, Nakamoto T, Hino K, Tsuji K, Shen ZJ, Nakashima K, et al. The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation. J Exp Med. 2005;201:961-70.
87. Shah R, Alvarez M, Jones DR, Torrungruang K, Watt AJ, Selvamurugan N, et al. Nmp4/CIZ regulation of matrix metalloproteinase 13 (MMP-13) response to parathyroid hormone in osteoblasts. Am J Physiol Endocrinol Metab. 2004;287:E289-96.
88. Thunyakitpisal P, Alvarez M, Tokunaga K, Onyia JE, Hock J, Ohashi N, et al. Cloning and functional analysis of a family of nuclear matrix transcription factors (NP/NMP4) that regulate type I collagen expression in osteoblasts. J Bone Miner Res. 2001;16:10-23.
89. Janssen H, Marynen P. Interaction partners for human ZNF384/CIZ/NMP4 - zyxin as a mediator for p130CAS signaling? Exp Cell Res. 312:1194-204.
90. Yang Z, Bidwell JP, Young SR, Gerard-O'Riley R, Wang H, Pavalko FM. Nmp4/CIZ inhibits mechanically induced beta-catenin signaling activity in osteoblasts. J Cell Physiol. 2010;223:435-41.