Abstract
Bone is the main component of the skeleton, together with connecting tissues including cartilage, ligaments and tendons, providing mechanical and structural support for the remaining organs and systems in the body. This mechanical and structural support function is indispensable for life, both during the growth and development period as well as during adult life. However, bone also provides the unique architecture and microenvironment that preserve the niches which maintain immature stem cells. This niche aspect of bone is an inadequately recognized function, although an essential one, since stem cells are required for tissue repair and regeneration during adult life. In addition to providing mechanical support, bone contains and supports the main reservoir of cells needed to sustain tissue integrity and function throughout our lives. Thus, understanding how bone is made and maintained during life is central to develo** adequate strategies to preserve a healthy skeleton as we age, so that proper mechanical support, structural integrity and tissue repair capacity are maintained.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Olsen BR, Reginato AM, Wang W. Bone development. Annu Rev Cell Dev Biol. 2000;16:191–220.
Pechak DG, Kujawa MJ, Caplan AI. Morphological and histochemical events during first bone formation in embryonic chick limbs. Bone. 1986;7:441–58.
Shapiro IM, Landis WJ, Risbud MV. Matrix vesicles: are they anchored exosomes? Bone. 2015;79:29–36.
Foster JW, Dominguez-Steglich MA, Guioli S, et al. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994;372:525–30.
Wagner T, Wirth J, Meyer J, et al. Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994;79:1111–20.
Bi W, Deng JM, Zhang Z, et al. Sox9 is required for cartilage formation. Nat Genet. 1999;22:85–9.
Iyama K, Ninomiya Y, Olsen BR, et al. Spatiotemporal pattern of type X collagen gene expression and collagen deposition in embryonic chick vertebrae undergoing endochondral ossification. Anat Rec. 1991;229:462–72.
Gerber HP, Vu TH, Ryan AM, et al. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med. 1999;5:623–8.
Park SR, Oreffo RO, Triffitt JT. Interconversion potential of cloned human marrow adipocytes in vitro. Bone. 1999;24:549–54.
Doherty MJ, Ashton BA, Walsh S, et al. Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res. 1998;13:828–38.
Schiller PC, D’Ippolito G, Brambilla R, et al. Inhibition of gap-junctional communication induces the trans-differentiation of osteoblasts to an adipocytic phenotype in vitro. J Biol Chem. 2001;276:14133–8.
Dallas SL, Bonewald LF. Dynamics of the transition from osteoblasts to osteocyte. Ann N Y Acad Sci. 2010;1192:437–43 (mini-review).
Compton JT, Lee FY. A review of osteocyte function and the emerging importance of sclerostin. J Bone Joint Surg. 2014;96:1659–68 (review).
Holtrop ME. The ultrastructure of bone. Ann Clin Lab Sci. 1975;5:264–71.
Parfitt AM. The actions of parathyroid hormone on bone: relation to bone remodeling and turnover, calcium homeostasis, and metabolic bone disease. Part I of IV parts: mechanisms of calcium transfer between blood and bone and their cellular basis: morphological and kinetic approaches to bone turnover. Metabolism. 1976;25:809–44.
Zhang D, Weinbaum S, Cowin SC. Electrical signal transmission in a bone cell network: the influence of a discrete gap junction. Ann Biomed Eng. 1998;26:644–59.
Zhang D, Cowin SC, Weinbaum S. Electrical signal transmission and gap junction regulation in a bone cell network: a cable model for an osteon. Ann Biomed Eng. 1997;25:357–74.
Schiller PC, Mehta PP, Roos BA, et al. Hormonal regulation of intercellular communication: parathyroid hormone increases connexin 43 gene expression and gap-junctional communication in osteoblastic cells. Mol Endocrinol. 1992;6:1433–40.
Schiller PC, D’Ippolito G, Roos BA, et al. Anabolic or catabolic responses of MC3T3-E1 osteoblastic cells to parathyroid hormone depend on time and duration of treatment. J Bone Miner Res. 1999;14:1504–12.
Schiller PC, D’Ippolito G, Balkan W, et al. Gap-junctional communication mediates parathyroid hormone stimulation of mineralization in osteoblastic cultures. Bone. 2001;28:38–44.
Schiller PC, D’Ippolito G, Balkan W, et al. Gap-junctional communication is required for the maturation process of osteoblastic cells in culture. Bone. 2001;28:362–9.
Civitelli R, Beyer EC, Warlow PM, et al. Connexin43 mediates direct intercellular communication in human osteoblastic cell networks. J Clin Invest. 1993;91:1888–96.
Lecanda F, Warlow PM, Sheikh S, et al. Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction. J Cell Biol. 2000;151:931–44.
Furlan F, Lecanda F, Screen J, et al. Proliferation, differentiation and apoptosis in connexin43-null osteoblasts. Cell Commun Adhes. 2001;8:367–71.
Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem. 2002;277:8648–57.
Noble BS, Stevens H, Loveridge N, et al. Identification of apoptotic changes in osteocytes in normal and pathological human bone. Bone. 1997;20:273–82.
Noble BS, Peet N, Stevens HY, et al. Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol. 2003;284:C934–43.
Plotkin LI, Aguirre JI, Kousteni S, et al. Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem. 2005;280:7317–25.
Plotkin LI, Mathov I, Aguirre JI, et al. Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. Am J Physiol Cell Physiol. 2005;289:C633–43.
Ducy P, Zhang R, Geoffroy V, et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747–54.
Otto F, Thornell AP, Crompton T, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 1997;89:765–71.
Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755–64.
Mundlos S, Otto F, Mundlos C, et al. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell. 1997;89:773–9.
Ducy P, Starbuck M, Priemel M, et al. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev. 1999;13:1025–36.
Kim S, Koga T, Isobe M, et al. Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev. 2003;17:1979–91.
Lee KS, Hong SH, Bae SC. Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein. Oncogene. 2002;21:7156–63.
Zhang YW, Yasui N, Ito K, et al. A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc Natl Acad Sci U S A. 2000;97:10549–54.
Alliston T, Choy L, Ducy P, et al. TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J. 2001;20:2254–72.
Zamurovic N, Cappellen D, Rohner D, et al. Coordinated activation of notch, Wnt, and transforming growth factor-beta signaling pathways in bone morphogenic protein 2-induced osteogenesis. Notch target gene Hey1 inhibits mineralization and Runx2 transcriptional activity. J Biol Chem. 2004;279:37704–15.
Sowa H, Kaji H, Hendy GN, et al. Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem. 2004;279:40267–75.
Sierra J, Villagra A, Paredes R, et al. Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity. Mol Cell Biol. 2003;23:3339–51.
Wang W, Wang YG, Reginato AM, et al. Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice. Dev Biol. 2004;270:364–81.
Bialek P, Kern B, Yang X, et al. A twist code determines the onset of osteoblast differentiation. Dev Cell. 2004;6:423–35.
Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17–29.
Akiyama Ddagger H, Kim Ddagger JE, Nakashima K, et al. Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. Proc Natl Acad Sci U S A. 2005;102:14665–70.
Huang LF, Fukai N, Selby PB, et al. Mouse clavicular development: analysis of wild-type and cleidocranial dysplasia mutant mice. Dev Dyn. 1997;210:33–40.
Inada M, Yasui T, Nomura S, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999;214:279–90.
Kim IS, Otto F, Zabel B, et al. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999;80:159–70.
Jimenez MJ, Balbin M, Lopez JM, et al. Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation. Mol Cell Biol. 1999;19:4431–42.
Porte D, Tuckermann J, Becker M, et al. Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone. Oncogene. 1999;18:667–78.
Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.
Church VL, Francis-West P. Wnt signalling during limb development. Int J Dev Biol. 2002;46:927–36.
Boyden LM, Mao J, Belsky J, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;346:1513–21.
Little RD, Recker RR, Johnson ML. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;347:943–4; author reply -4.
Kato M, Patel MS, Levasseur R, et al. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol. 2002;157:303–14.
Holmen SL, Zylstra CR, Mukherjee A, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005;280:21162–8.
Day TF, Guo X, Garrett-Beal L, et al. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 2005;8:739–50.
Hill TP, Spater D, Taketo MM, et al. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005;8:727–38.
Hu H, Hilton MJ, Tu X, et al. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development. 2005;132:49–60.
Canalis E. Wnt signaling in osteoporosis: mechanisms and novel therapeutic approaches. Nat Rev Endocrinol. 2013;9:575–83.
Mannstadt M, Juppner H, Gardella TJ. Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol. 1999;277:F665–75.
Swarthout JT, D’Alonzo RC, Selvamurugan N, et al. Parathyroid hormone-dependent signaling pathways regulating genes in bone cells. Gene. 2002;282:1–17.
Qin L, Qiu P, Wang L, et al. Gene expression profiles and transcription factors involved in parathyroid hormone signaling in osteoblasts revealed by microarray and bioinformatics. J Biol Chem. 2003;278:19723–31.
Wang BL, Dai CL, Quan JX, et al. Parathyroid hormone regulates osterix and Runx2 mRNA expression predominantly through protein kinase A signaling in osteoblast-like cells. J Endocrinol Invest. 2006;29:101–8.
Locklin RM, Khosla S, Turner RT, et al. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. J Cell Biochem. 2003;89:180–90.
Mikuni-Takagaki Y, Naruse K, Azuma Y, et al. The role of calcium channels in osteocyte function. J Musculoskelet Neuronal Interact. 2002;2:252–5.
Sekiya H, Mikuni-Takagaki Y, Kondoh T, et al. Synergistic effect of PTH on the mechanical responses of human alveolar osteocytes. Biochem Biophys Res Commun. 1999;264:719–23.
Chen X, Macica CM, Ng KW, et al. Stretch-induced PTH-related protein gene expression in osteoblasts. J Bone Miner Res. 2005;20:1454–61.
D’Ippolito G, Schiller PC, Perez-stable C, et al. Cooperative actions of hepatocyte growth factor and 1,25-dihydroxyvitamin D3 in osteoblastic differentiation of human vertebral bone marrow stromal cells. Bone. 2002;31:269–75.
D’Ippolito G, Diabira S, Howard GA, et al. Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells. Bone. 2006;39:513–22.
Erben RG, Soegiarto DW, Weber K, et al. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol Endocrinol. 2002;16:1524–37.
Paredes R, Arriagada G, Cruzat F, et al. Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells. Mol Cell Biol. 2004;24:8847–61.
Haussler MR, Whitfield GK, Kaneko I, et al. Molecular mechanisms of vitamin D action. Calcif Tissue Int. 2013;92:77–98 (review).
Jones G. Vitamin D, analogs. Endocrinol Metab Clin North Am. 2010;39:447–72 (review).
Curtis KM, Aenlle KK, Roos BA, Howard GA. 24R,25-dihydroxyvitamin D3 promotes the osteoblastic differentiation of human mesenchymal stem cells. Mol Endocrinol. 2014;28:644–58.
Ucer S, Iyer S, Bartell SM, et al. The effects of androgens on murine cortical bone do not require AR or ERα signaling in osteoblasts and osteoclasts. J Bone Miner Res. 2015;30:1138–49.
Pan W, Quarles LD, Song LH, et al. Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture. J Cell Biochem. 2005;94:307–16.
Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci. 2006;1068:173–9.
Seeman E. Estrogen, androgen, and the pathogenesis of bone fragility in women and men. Curr Osteoporos Rep. 2004;2:90–6.
Jessop HL, Sjoberg M, Cheng MZ, et al. Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. J Bone Miner Res. 2001;16:1045–55.
Zaman G, Jessop HL, Muzylak M, et al. Osteocytes use estrogen receptor alpha to respond to strain but their ERalpha content is regulated by estrogen. J Bone Miner Res. 2006;21:1297–306.
Melville KM, Kelly NH, Surita G, et al. Effects of deletion of ERα in osteoblast-lineage cells on bone mass and adaptation to mechanical loading differ in female and male mice. J Bone Miner Res. 2015;30:1468–80.
Li X, Cao X. BMP signaling and skeletogenesis. Ann N Y Acad Sci. 2006;1068:26–40.
Zaidi SK, Sullivan AJ, van Wijnen AJ, et al. Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci U S A. 2002;99:8048–53.
Afzal F, Pratap J, Ito K, et al. Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription. J Cell Physiol. 2005;204:63–72.
Lee MH, Kim YJ, Kim HJ, et al. BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression. J Biol Chem. 2003;278:34387–94.
Ryoo HM, Lee MH, Kim YJ. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene. 2006;366:51–7.
Li T, Surendran K, Zawaideh MA, et al. Bone morphogenetic protein 7: a novel treatment for chronic renal and bone disease. Curr Opin Nephrol Hypertens. 2004;13:417–22.
Spencer EM, Liu CC, Si ECC, Howard GA. In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in Rats. Bone. 1991;12:21–6.
Green ED, Maffei M, Braden VV, et al. The human obese (OB) gene: RNA expression pattern and map** on the physical, cytogenetic, and genetic maps of chromosome 7. Genome Res. 1995;5:5–12.
Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1:1155–61.
Wolf G. Leptin: the weight-reducing plasma protein encoded by the obese gene. Nutr Rev. 1996;54:91–3.
Steppan CM, Crawford DT, Chidsey-Frink KL, et al. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept. 2000;92:73–8.
Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100:197–207.
Shi Y, Yadav VK, Suda N, et al. Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo. Proc Natl Acad Sci U S A. 2008;105:20529–33.
Hess R, Pino AM, Rios S, et al. High affinity leptin receptors are present in human mesenchymal stem cells (MSCs) derived from control and osteoporotic donors. J Cell Biochem. 2005;94:50–7.
Zheng B, Jiang J, Luo K, et al. Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin. Cell Tissue Res. 2015. doi:10.1007/s00441-01502167-y.
Canalis E. Mechanisms of glucocorticoid action in bone. Curr Osteoporos Rep. 2005;3:98–102.
Ohnaka K, Taniguchi H, Kawate H, et al. Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: novel mechanism of glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun. 2004;318:259–64.
Ohnaka K, Tanabe M, Kawate H, et al. Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts. Biochem Biophys Res Commun. 2005;329:177–81.
Bassett JH, Williams GR. The molecular actions of thyroid hormone in bone. Trends Endocrinol Metab. 2003;14:356–64.
Stevens DA, Hasserjian RP, Robson H, et al. Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation. J Bone Miner Res. 2000;15:2431–42.
Robson H, Siebler T, Stevens DA, et al. Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation. Endocrinology. 2000;141:3887–97.
Gruber R, Czerwenka K, Wolf F, et al. Expression of the vitamin D receptor, of estrogen and thyroid hormone receptor alpha- and beta-isoforms, and of the androgen receptor in cultures of native mouse bone marrow and of stromal/osteoblastic cells. Bone. 1999;24:465–73.
Salto C, Kindblom JM, Johansson C, et al. Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice. Mol Endocrinol. 2001;15:2115–28.
Pereira RC, Jorgetti V, Canalis E. Triiodothyronine induces collagenase-3 and gelatinase B expression in murine osteoblasts. Am J Physiol. 1999;277:E496–504.
Fang S, Deng Y, Gu P, Fan X. MicroRNAs regulate bone development and regeneration. Int J Mol Sci. 2015;16:8227–53 (review).
Engsig MT, Chen QJ, Vu TH, et al. Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into develo** long bones. J Cell Biol. 2000;151:879–89.
Tondravi MM, McKercher SR, Anderson K, et al. Osteopetrosis in mice lacking haematopoietic transcription factor PU.1. Nature. 1997;386:81–4.
DeKoter RP, Singh H. Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science. 2000;288:1439–41.
Luchin A, Suchting S, Merson T, et al. Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J Biol Chem. 2001;276:36703–10.
Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89:309–19.
Dai XM, Ryan GR, Hapel AJ, et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood. 2002;99:111–20.
Blair HC, Zaidi M. Osteoclastic differentiation and function regulated by old and new pathways. Rev Endocr Metab Disord. 2006;7:23–32.
Choi SJ, Han JH, Roodman GD. ADAM8: a novel osteoclast stimulating factor. J Bone Miner Res. 2001;16:814–22.
Rao H, Lu G, Kajiya H, et al. Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function. J Bone Miner Res. 2006;21:1657–65.
Kobayashi Y, Uehara S, Koide M, Takahaski N. The regulation of osteoclasts differentiation by Wnt signals. BonKEy Rep. 2015;4, Article number:713 (review).
Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev. 1994;15:439–61.
McKane WR, Khosla S, Egan KS, et al. Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption. J Clin Endocrinol Metab. 1996;81:1699–703.
Khosla S, Melton 3rd LJ, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. 1998;83:2266–74.
Eastell R, Simmons PS, Colwell A, et al. Nyctohemeral changes in bone turnover assessed by serum bone Gla-protein concentration and urinary deoxypyridinoline excretion: effects of growth and ageing. Clin Sci (Lond). 1992;83:375–82.
Duda Jr RJ, O’Brien JF, Katzmann JA, et al. Concurrent assays of circulating bone Gla-protein and bone alkaline phosphatase: effects of sex, age, and metabolic bone disease. J Clin Endocrinol Metab. 1988;66:951–7.
Vidal C, Bermeo S, Fatkin D, Duque G. Role of the nuclear envelope in the pathogenesis of age-related bone loss and osteoporosis. BoneKEy Rep. 2012;1, Article number:62 (review).
Pacheco LM, Gomez LA, Dias J, et al. Progerin expression disrupts critical adult stem cell functions involved in tissue repair. Aging. 2014;6:1049–63.
Riggs BL, Wahner HW, Seeman E, et al. Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes. J Clin Invest. 1982;70:716–23.
Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.
Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.
Adams GB, Martin RP, Alley IR, et al. Therapeutic targeting of a stem cell niche. Nat Biotechnol. 2007;25:238–43.
Yin T, Li L. The stem cell niches in bone. J Clin Invest. 2006;116:1195–201.
Kiel MJ, Yilmaz OH, Iwashita T, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–21.
Cipolleschi MG, Dello Sbarba P, Olivotto M. The role of hypoxia in the maintenance of hematopoietic stem cells. Blood. 1993;82:2031–7.
Cipolleschi MG, D’Ippolito G, Bernabei PA, et al. Severe hypoxia enhances the formation of erythroid bursts from human cord blood cells and the maintenance of BFU-E in vitro. Exp Hematol. 1997;25:1187–94.
Reyes M, Lund T, Lenvik T, et al. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 2001;98:2615–25.
D’Ippolito G, Howard GA, Roos BA, et al. Isolation and characterization of marrow-isolated adult multilineage inducible (MIAMI) cells. Exp Hematol. 2006;34:1608–10.
D’Ippolito G, Diabira S, Howard GA, et al. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci. 2004;117:2971–81.
Breyer A, Estharabadi N, Oki M, et al. Multipotent adult progenitor cell isolation and culture procedures. Exp Hematol. 2006;34:1596–601.
Paquet J, Deschepper M, Moya A, et al. Oxygen tension regulates human mesenchymal stem cell paracrine functions. Stem Cells Transl Med. 2015;4:809–21.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Howard, G.A., Schiller, P.C. (2016). Biology of Bone. In: Duque, G., Kiel, D. (eds) Osteoporosis in Older Persons. Springer, Cham. https://doi.org/10.1007/978-3-319-25976-5_1
Download citation
DOI: https://doi.org/10.1007/978-3-319-25976-5_1
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-25974-1
Online ISBN: 978-3-319-25976-5
eBook Packages: MedicineMedicine (R0)