Skip to main content
SpringerLink
Log in

Basic Aspects of Osteoblast Function

  • Chapter
  • First Online:
Osteoporosis

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

The cells of the osteoblast lineage (osteoblasts, osteocytes, and bone lining cells) have multiple stage-specific functions in the skeleton, including formation of the bone matrix. They arise from pluripotent mesenchymal progenitors, which can also give rise to adipocytes and chondrocytes. The functions carried out by the osteoblast lineage are regulated by both paracrine and endocrine factors. During bone formation, osteoblasts produce the collagenous matrix (osteoid), which becomes mineralized through the deposition and accumulation of bioapatite mineral crystals; the latter is dependent on the availability of inorganic phosphate, which is regulated by the osteoblast lineage through production of alkaline phosphatase, and other non-collagenous proteins. During osteoid deposition, osteoblasts can become embedded within their own matrix, and differentiate further, to become interconnected osteocytes. Alternatively, they may remain on the surface as bone lining cells, which have the potential to become reactivated into matrix-producing osteoblasts. The osteoblast lineage also supports osteoclast formation and thereby regulates bone resorption through the production of receptor activator of NF-ΚB ligand (RANKL), colony-stimulating factor 1 (CSF-1), and osteoprotegerin (OPG), a decoy receptor for RANKL. This versatile cell lineage therefore not only forms bone but can also controls its removal, which makes understanding the stage-specific roles of the osteoblast lineage crucial for targeting many skeletal conditions, such as osteoporosis, osteogenesis imperfecta, and other pathological conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sims NA. Cell-specific paracrine actions of IL-6 family cytokines from bone, marrow and muscle that control bone formation and resorption. Int J Biochem Cell Biol. 2016;79:14–23.

    Article  CAS  PubMed  Google Scholar 

  2. Tonna S, Sims NA. Talking among ourselves: paracrine control of bone formation within the osteoblast lineage. Calcif Tissue Int. 2014;94(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  3. Martin TJ, Sims NA. Integrating endocrine and paracrine influences on bone: lessons from parathyroid hormone and parathyroid homrone-related protein. In: Thakker RW, Whyte MP, Eisman JA, Igarashi T, editors. Genetics of bone biology and skeletal disease. New York: Academic Press; 2013.

    Google Scholar 

  4. Abdelgawad ME, Delaisse J-M, Hinge M, Jensen PR, Alnaimi RW, Rolighed L, et al. Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts. Histochem Cell Biol. 2016;145(6):603–15.

    Article  CAS  PubMed  Google Scholar 

  5. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425(6960):841–6.

    Article  CAS  PubMed  Google Scholar 

  6. Askmyr M, Sims NA, Martin TJ, Purton LE. What is the true nature of the osteoblastic hematopoietic stem cell niche? Trends Endocrinol Metab. 2009;20(6):303–9.

    Article  CAS  PubMed  Google Scholar 

  7. Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wu JY, Purton LE, Rodda SJ, Chen M, Weinstein LS, McMahon AP, et al. Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways. Proc Natl Acad Sci U S A. 2008;105(44):16976–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fukumoto S, Martin TJ. Bone as an endocrine organ. Trends Endocrinol Metab. 2009;20(5):230–6.

    Article  CAS  PubMed  Google Scholar 

  10. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell. 2008;2(4):313–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sacchetti B, Funari A, Remoli C, Giannicola G, Kogler G, Liedtke S, et al. No identical "mesenchymal stem cells" at different times and sites: human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels. Stem Cell Rep. 2016;6(6):897–913.

    Article  CAS  Google Scholar 

  13. Kalajzic Z, Li H, Wang LP, Jiang X, Lamothe K, Adams DJ, et al. Use of an alpha-smooth muscle actin GFP reporter to identify an osteoprogenitor population. Bone. 2008;43(3):501–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brighton CT, Lorich DG, Kupcha R, Reilly TM, Jones AR, Woodbury RA 2nd. The pericyte as a possible osteoblast progenitor cell. Clin Orthop Relat Res. 1992;275:287–99.

    Google Scholar 

  15. Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE. Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Min Res: Off J Am Soc Bone Min Res. 1998;13(5):828–38.

    Article  CAS  Google Scholar 

  16. Bianco P, Robey PG. Skeletal stem cells. Development. 2015;142(6):1023–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Colnot C, Lu C, Hu D, Helms JA. Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol. 2004;269(1):55–69.

    Article  CAS  PubMed  Google Scholar 

  18. Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI, Mackem S, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010;19(2):329–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhou X, von der Mark K, Henry S, Norton W, Adams H, de Crombrugghe B. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet. 2014;10(12):e1004820.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Roach HI. Trans-differentiation of hypertrophic chondrocytes into cells capable of producing a mineralized bone matrix. Bone Miner. 1992;19(1):1–20.

    Article  CAS  PubMed  Google Scholar 

  21. Matic I, Matthews BG, Wang X, Dyment NA, Worthley DL, Rowe DW, et al. Quiescent bone lining cells are a major source of osteoblasts during adulthood. Stem Cells. 2016;34(12):2930–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Torreggiani E, Matthews BG, Pejda S, Matic I, Horowitz MC, Grcevic D, et al. Preosteocytes/osteocytes have the potential to dedifferentiate becoming a source of osteoblasts. PLoS One. 2013;8(9):e75204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ducy P, Starbuck M, Priemel M, Shen J, Pinero G, Geoffroy V, et al. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev. 1999;13(8):1025–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108(1):17–29.

    Article  CAS  PubMed  Google Scholar 

  25. Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for coffin-Lowry syndrome. Cell. 2004;117(3):387–98.

    Article  CAS  PubMed  Google Scholar 

  26. Sabatakos G, Sims NA, Chen J, Aoki K, Kelz MB, Amling M, et al. Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis. Nat Med. 2000;6(9):985–90.

    Article  CAS  PubMed  Google Scholar 

  27. Gutierrez S, Javed A, Tennant DK, van Rees M, Montecino M, Stein GS, et al. 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. 2002;277(2):1316–23.

    Article  CAS  PubMed  Google Scholar 

  28. Komori T. Regulation of osteoblast differentiation by transcription factors. J Cell Biochem. 2006;99(5):1233–9.

    Article  CAS  PubMed  Google Scholar 

  29. Christy RJ, Yang VW, Ntambi JM, Geiman DE, Landschulz WH, Friedman AD, et al. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev. 1989;3(9):1323–35.

    Article  CAS  PubMed  Google Scholar 

  30. Tanaka T, Yoshida N, Kishimoto T, Akira S. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J. 1997;16(24):7432–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME. Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci. 1992;102(Pt 2):341–51.

    CAS  PubMed  Google Scholar 

  32. Sims NA, Clement-Lacroix P, Da Ponte F, Bouali Y, Binart N, Moriggl R, et al. Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5. J Clin Invest. 2000;106(9):1095–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Walker EC, McGregor NE, Poulton IJ, Solano M, Pompolo S, Fernandes TJ, et al. Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J Clin Invest. 2010;120(2):582–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Poulton IJ, McGregor NE, Pompolo S, Walker EC, Sims NA. Contrasting roles of leukemia inhibitory factor in murine bone development and remodeling involve region-specific changes in vascularization. J Bone Miner Res. 2012;27(3):586–95.

    Article  CAS  PubMed  Google Scholar 

  35. Martin RB, Chow BD, Lucas PA. Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs. Calcif Tissue Int. 1990;46(3):189–94.

    Article  CAS  PubMed  Google Scholar 

  36. Chen C, Kalu DN. Strain differences in bone density and calcium metabolism between c3h/hej and c57bl/6j mice. Bone. 1999;25(4):413–20.

    Article  CAS  PubMed  Google Scholar 

  37. Horowitz MC, Berry R, Holtrup B, Sebo Z, Nelson T, Fretz JA, et al. Bone marrow adipocytes. Adipocytes. 2017;6(3):193–204.

    Article  CAS  Google Scholar 

  38. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology. 2001;2(3):165–71.

    Article  CAS  PubMed  Google Scholar 

  39. Inada M, Yasui T, Nomura S, Miyake S, Deguchi K, Himeno M, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999;214(4):279–90.

    Article  CAS  PubMed  Google Scholar 

  40. Kim IS, Otto F, Zabel B, Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999;80(2):159–70.

    Article  CAS  PubMed  Google Scholar 

  41. Nishimura R, Wakabayashi M, Hata K, Matsubara T, Honma S, Wakisaka S, et al. Osterix regulates calcification and degradation of chondrogenic matrices through matrix metalloproteinase 13 (MMP13) expression in association with transcription factor Runx2 during endochondral ossification. J Biol Chem. 2012;287(40):33179–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Komori T. Runx2, an inducer of osteoblast and chondrocyte differentiation. Histochem Cell Biol. 2018;149(4):313–23.

    Article  CAS  PubMed  Google Scholar 

  43. Ecarot-Charrier B, Glorieux FH, van der Rest M, Pereira G. Osteoblasts isolated from mouse calvaria initiate matrix mineralization in culture. J Cell Biol. 1983;96(3):639–43.

    Article  CAS  PubMed  Google Scholar 

  44. Abe Y, Akamine A, Aida Y, Maeda K. Differentiation and mineralization in osteogenic precursor cells derived from fetal rat mandibular bone. Calcif Tissue Int. 1993;52(5):365–71.

    Article  CAS  PubMed  Google Scholar 

  45. Gerber I, ap Gwynn I. Influence of cell isolation, cell culture density, and cell nutrition on differentiation of rat calvarial osteoblast-like cells in vitro. Eur Cell Mater. 2001;2:10–20.

    Article  CAS  PubMed  Google Scholar 

  46. Martin TJ, Sims NA. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005;11(2):76–81.

    Article  CAS  PubMed  Google Scholar 

  47. Sims NA, Martin TJ. Coupling signals between the osteoclast and osteoblast: how are messages transmitted between these temporary visitors to the bone surface? Front Endocrinol (Lausanne). 2015;6:41.

    Article  Google Scholar 

  48. Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3:481.

    PubMed  PubMed Central  Google Scholar 

  49. Aubin JE. Advances in the osteoblast lineage. Biochem Cell Biol. 1998;76(6):899–910.

    Article  CAS  PubMed  Google Scholar 

  50. Stein GS, Lian JB, Owen TA. Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J. 1990;4(13):3111–23.

    Article  CAS  PubMed  Google Scholar 

  51. Bellido T, Stahl N, Farruggella TJ, Borba V, Yancopoulos GD, Manolagas SC. Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells. J Clin Invest. 1996;97(2):431–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Aubin JE, Liu F, Malaval L, Gupta AK. Osteoblast and chondroblast differentiation. Bone. 1995;17(2 Suppl):77S–83S.

    Article  CAS  PubMed  Google Scholar 

  53. Buenzli PR, Sims NA. Quantifying the osteocyte network in the human skeleton. Bone. 2015;75:144–50.

    Article  CAS  PubMed  Google Scholar 

  54. Franz-Odendaal TA, Hall BK, Witten PE. Buried alive: how osteoblasts become osteocytes. Dev Dyn. 2006;235(1):176–90.

    Article  CAS  PubMed  Google Scholar 

  55. Palumbo C, Palazzini S, Marotti G. Morphological study of intercellular junctions during osteocyte differentiation. Bone. 1990;11(6):401–6.

    Article  CAS  PubMed  Google Scholar 

  56. Dudley HR, Spiro D. The fine structure of bone cells. J Biophys Biochem Cytol. 1961;11(3):627–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Schaffler MB, Cheung WY, Majeska R, Kennedy O. Osteocytes: master orchestrators of bone. Calcif Tissue Int. 2014;94(1):5–24.

    Article  CAS  PubMed  Google Scholar 

  58. van Bezooijen RL, Roelen BA, Visser A, Van der Wee-Pals L, de Wilt E, Karperien M, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199(6):805–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Toyosawa S, Shintani S, Fujiwara T, Ooshima T, Sato A, Ijuhin N, et al. Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J Bone Min Res: Off J Am Soc Bone Min Res. 2001;16(11):2017–26.

    Article  CAS  Google Scholar 

  60. Gowen LC, Petersen DN, Mansolf AL, Qi H, Stock JL, Tkalcevic GT, et al. Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem. 2003;278(3):1998–2007.

    Article  CAS  PubMed  Google Scholar 

  61. Fukumoto S. FGF23-FGF receptor/klotho pathway as a new drug target for disorders of bone and mineral metabolism. Calcif Tissue Int. 2016;98(4):334–40.

    Article  CAS  PubMed  Google Scholar 

  62. Miller SC, de Saint-Georges L, Bowman BM, Jee WS. Bone lining cells: structure and function. Scanning Microsc 1989;3(3):953–960; discussion 60-1.

    Google Scholar 

  63. Jones SJ, Boyde A. Experimental study of changes in osteoblastic shape induced by calcitonin and parathyroid extract in an organ culture system. Cell Tissue Res. 1976;169(4):449–65.

    Article  Google Scholar 

  64. Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption--a hypothesis. Calcif Tissue Int. 1981;33(4):349–51.

    Article  CAS  PubMed  Google Scholar 

  65. Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Min Res: Off J Am Soc Bone Min Res. 2001;16(9):1575–82.

    Article  CAS  Google Scholar 

  66. Rasmussen HH, Bordier P. The physiological basis of metabolic bone disease Williams and Wilkins. Baltimore: Waverley Press; 1974.

    Google Scholar 

  67. Eriksen EF, Eghbali-Fatourechi GZ, Khosla S. Remodeling and vascular spaces in bone. J Bone Min Res: Off J Am Soc Bone Min Res. 2007;22(1):1–6.

    Article  CAS  Google Scholar 

  68. Kristensen HB, Andersen TL, Marcussen N, Rolighed L, Delaisse JM. Increased presence of capillaries next to remodeling sites in adult human cancellous bone. J Bone Miner Res. 2013;28(3):574–85.

    Article  CAS  PubMed  Google Scholar 

  69. Dobnig H, Turner RT. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology. 1995;136(8):3632–8.

    Article  CAS  PubMed  Google Scholar 

  70. Kim SW, Pajevic PD, Selig M, Barry KJ, Yang JY, Shin CS, et al. Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts. J Bone Min Res: Off J Am Soc Bone Min Res. 2012;27(10):2075–84.

    Article  CAS  Google Scholar 

  71. Chow JW, Wilson AJ, Chambers TJ, Fox SW. Mechanical loading stimulates bone formation by reactivation of bone lining cells in 13-week-old rats. J Bone Min Res: Off J Am Soc Bone Min Res. 1998;13(11):1760–7.

    Article  CAS  Google Scholar 

  72. Kim SW, Lu Y, Williams EA, Lai F, Lee JY, Enishi T, et al. Sclerostin antibody administration converts bone lining cells into active osteoblasts. J Bone Min Res: Off J Am Soc Bone Min Res. 2017;32(5):892–901.

    Article  CAS  Google Scholar 

  73. Fonseca H, Moreira-Gonçalves D, Coriolano H-JA, Duarte JA. Bone quality: the determinants of bone strength and fragility. Sports Med. 2014;44(1):37–53.

    Article  PubMed  Google Scholar 

  74. Ural A, Vashishth D. Hierarchical perspective of bone toughness–from molecules to fracture. Int Mater Rev. 2014;59(5):245–63.

    Article  CAS  Google Scholar 

  75. Fratzl P, Gupta H, Paschalis E, Roschger P. Structure and mechanical quality of the collagen–mineral nano-composite in bone. J Mater Chem. 2004;14(14):2115–23.

    Article  CAS  Google Scholar 

  76. Genet F, Kulina I, Vaquette C, Torossian F, Millard S, Pettit AR, et al. Neurological heterotopic ossification following spinal cord injury is triggered by macrophage-mediated inflammation in muscle. J Pathol. 2015;236(2):229–40.

    Article  CAS  PubMed  Google Scholar 

  77. Convente MR, Chakkalakal SA, Yang E, Caron RJ, Zhang D, Kambayashi T, et al. Depletion of mast cells and macrophages impairs heterotopic ossification in an Acvr1(R206H) mouse model of Fibrodysplasia Ossificans Progressiva. J Bone Miner Res. 2018;33(2):269–82.

    Article  CAS  PubMed  Google Scholar 

  78. Weiner S, Wagner HD. The material bone: structure-mechanical function relations. Annu Rev Mater Sci. 1998;28(1):271–98.

    Article  CAS  Google Scholar 

  79. Giraud-Guille MM. Twisted plywood architecture of collagen fibrils in human compact bone osteons. Calcif Tissue Int. 1988;42(3):167–80.

    Article  CAS  PubMed  Google Scholar 

  80. Su X, Feng Q, Cui F, Zhu X. Microstructure and micromechanical properties of the mid-diaphyses of human fetal femurs. Connect Tissue Res. 1997;36(3):271–86.

    Article  CAS  PubMed  Google Scholar 

  81. Hosaki-Takamiya R, Hashimoto M, Imai Y, Nishida T, Yamada N, Mori H, et al. Collagen production of osteoblasts revealed by ultra-high voltage electron microscopy. J Bone Miner Metab. 2016;34(5):491–9.

    Article  CAS  PubMed  Google Scholar 

  82. Lu Y, Kamel-El Sayed SA, Wang K, Tiede-Lewis LM, Grillo MA, Veno PA, et al. Live imaging of type I collagen assembly dynamics in osteoblasts stably expressing GFP and mCherry-Tagged collagen constructs. J Bone Min Res. 2018;33(6):1166–82.

    Article  CAS  Google Scholar 

  83. Brodsky B, Ramshaw JA. The collagen triple-helix structure. Matrix Biol. 1997;15(8–9):545–54.

    Article  CAS  PubMed  Google Scholar 

  84. Leblond CP. Synthesis and secretion of collagen by cells of connective tissue, bone, and dentin. Anat Rec. 1989;224(2):123–38.

    Article  CAS  PubMed  Google Scholar 

  85. Viguet-Carrin S, Garnero P, Delmas P. The role of collagen in bone strength. Osteoporos Int. 2006;17(3):319–36.

    Article  CAS  PubMed  Google Scholar 

  86. Oxlund H, Barckman M, Ørtoft G, Andreassen TT. Reduced concentrations of collagen cross-links are associated with reduced strength of bone. Bone. 1995;17(4, Supplement):S365–S71.

    Article  Google Scholar 

  87. Vashishth D, Gibson GJ, Khoury JI, Schaffler MB, Kimura J, Fyhrie DP. Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone. 2001;28(2):195–201.

    Article  CAS  PubMed  Google Scholar 

  88. Forlino A, Marini JC. Osteogenesis imperfecta. Lancet. 2016;387(10028):1657–71.

    Article  CAS  PubMed  Google Scholar 

  89. Glimcher M. The natuer of the mineral phase in bone: biological and clinical implications. In: Avioli L, Krane S, editors. Metabolic bone disease, vol. 23. San Diego: Academic Press; 1998. p. 50.

    Google Scholar 

  90. Ruffoni D, Fratzl P, Roschger P, Klaushofer K, Weinkamer R. The bone mineralization density distribution as a fingerprint of the mineralization process. Bone. 2007;40(5):1308–19.

    Article  CAS  PubMed  Google Scholar 

  91. Boivin G, Meunier PJ. The degree of mineralization of bone tissue measured by computerized quantitative contact microradiography. Calcif Tissue Int. 2002;70(6):503–11.

    Article  CAS  PubMed  Google Scholar 

  92. Fuchs RK, Allen MR, Ruppel ME, Diab T, Phipps RJ, Miller LM, et al. In situ examination of the time-course for secondary mineralization of Haversian bone using synchrotron Fourier transform infrared microspectroscopy. Matrix Biol. 2008;27(1):34–41.

    Article  CAS  PubMed  Google Scholar 

  93. Vrahnas C, Pearson TA, Brunt AR, Forwood MR, Bambery KR, Tobin MJ, et al. Anabolic action of parathyroid hormone (PTH) does not compromise bone matrix mineral composition or maturation. Bone. 2016;93:146–54.

    Article  CAS  PubMed  Google Scholar 

  94. Vrahnas C, Buenzli PR, Pearson TA, Pennypacker BL, Tobin MJ, Bambery KR, et al. Differing effects of parathyroid hormone, alendronate and Odanacatib on bone formation and on the mineralisation process in intracortical and endocortical bone of ovariectomized rabbits. Calcif Tissue Int. 2018;103(6):625–37.

    Article  CAS  PubMed  Google Scholar 

  95. Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. Bonekey Rep. 2013;2:447.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Anderson HC. Molecular biology of matrix vesicles. Clin Orthop Relat Res. 1995;314:266–80.

    Google Scholar 

  97. Hoshi K, Ozawa H. Matrix vesicle calcification in bones of adult rats. Calcif Tissue Int. 2000;66(6):430–4.

    Article  CAS  PubMed  Google Scholar 

  98. Rohde M, Mayer H. Exocytotic process as a novel model for mineralization by osteoblasts in vitro and in vivo determined by electron microscopic analysis. Calcif Tissue Int. 2007;80(5):323–36.

    Article  CAS  PubMed  Google Scholar 

  99. Stanford CM, Jacobson PA, Eanes ED, Lembke LA, Midura RJ. Rapidly forming apatitic mineral in an osteoblastic cell line (UMR 106-01 BSP). J Biol Chem. 1995;270(16):9420–8.

    Article  CAS  PubMed  Google Scholar 

  100. Whyte MP. Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev. 1994;15(4):439–61.

    CAS  PubMed  Google Scholar 

  101. Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. 2003;285(1):E1–9.

    Article  CAS  PubMed  Google Scholar 

  102. Holm E, Aubin JE, Hunter GK, Beier F, Goldberg HA. Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization. Bone. 2015;71:145–54.

    Article  CAS  PubMed  Google Scholar 

  103. Boskey AL, Gadaleta S, Gundberg C, Doty SB, Ducy P, Karsenty G. Fourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin. Bone. 1998;23(3):187–96.

    Article  CAS  PubMed  Google Scholar 

  104. Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Goding JW, et al. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A. 2002;99(14):9445–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998;139(3):1329–37.

    Article  PubMed  Google Scholar 

  106. Horwood NJ, Elliott J, Martin TJ, Gillespie MT. Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology. 1998;139(11):4743–6.

    Article  CAS  PubMed  Google Scholar 

  107. Palmqvist P, Persson E, Conaway HH, Lerner UH. IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J Immunol. 2002;169(6):3353–62.

    Article  CAS  PubMed  Google Scholar 

  108. Liu BY, Guo J, Lanske B, Divieti P, Kronenberg HM, Bringhurst FR. Conditionally immortalized murine bone marrow stromal cells mediate parathyroid hormone-dependent osteoclastogenesis in vitro. Endocrinology. 1998;139(4):1952–64.

    Article  CAS  PubMed  Google Scholar 

  109. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4(8):638–49.

    Article  CAS  PubMed  Google Scholar 

  110. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 1999;20(3):345–57.

    Article  CAS  PubMed  Google Scholar 

  111. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402(6759):304–9.

    Article  CAS  PubMed  Google Scholar 

  112. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999;13(18):2412–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–19.

    Article  CAS  PubMed  Google Scholar 

  114. Tsuda E, Goto M, Mochizuki S, Yano K, Kobayashi F, Morinaga T, et al. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis. Biochem Biophys Res Commun. 1997;234(1):137–42.

    Article  CAS  PubMed  Google Scholar 

  115. Kartsogiannis V, Zhou H, Horwood NJ, Thomas RJ, Hards DK, Quinn JM, et al. Localization of RANKL (receptor activator of NF kappa B ligand) mRNA and protein in skeletal and extraskeletal tissues. Bone. 1999;25(5):525–34.

    Article  CAS  PubMed  Google Scholar 

  116. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun. 1999;265(1):144–50.

    Article  CAS  PubMed  Google Scholar 

  117. Soderstrom K, Stein E, Colmenero P, Purath U, Muller-Ladner U, de Matos CT, et al. Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis. Proc Natl Acad Sci U S A. 2010;107(29):13028–33.

    Article  CAS  PubMed  Google Scholar 

  118. Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, et al. RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. Ann Rheum Dis. 2016;75(6):1187–95.

    Article  CAS  PubMed  Google Scholar 

  119. Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17(10):1235–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Chia LY, Walsh NC, Martin TJ, Sims NA. Isolation and gene expression of haematopoietic-cell-free preparations of highly purified murine osteocytes. Bone. 2015;72:34–42.

    Article  CAS  PubMed  Google Scholar 

  121. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-Hora M, Feng JQ, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17(10):1231–4.

    Article  CAS  PubMed  Google Scholar 

  122. Fumoto T, Takeshita S, Ito M, Ikeda K. Physiological functions of osteoblast lineage and T cell-derived RANKL in bone homeostasis. J Bone Min Res: Off J Am Soc Bone Min Res. 2014;29(4):830–42.

    Article  CAS  Google Scholar 

  123. Takahashi N, Akatsu T, Udagawa N, Sasaki T, Yamaguchi A, Moseley JM, et al. Osteoblastic cells are involved in osteoclast formation. Endocrinology. 1988;123(5):2600–2.

    Article  CAS  PubMed  Google Scholar 

  124. Suda T, Takahashi N, Martin TJ. Modulation of osteoclast differentiation. Endocr Rev. 1992;13(1):66–80.

    CAS  PubMed  Google Scholar 

  125. Quinn JM, Itoh K, Udagawa N, Hausler K, Yasuda H, Shima N, et al. Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions. J Bone Miner Res. 2001;16(10):1787–94.

    Article  CAS  PubMed  Google Scholar 

  126. Tomimori Y, Mori K, Koide M, Nakamichi Y, Ninomiya T, Udagawa N, et al. Evaluation of pharmaceuticals with a novel 50-hour animal model of bone loss. J Bone Min Res: Off J Am Soc Bone Min Res. 2009;24(7):1194–205.

    Article  CAS  Google Scholar 

  127. Kamioka H, Honjo T, Takano-Yamamoto T. A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy. Bone. 2001;28(2):145–9.

    Article  CAS  PubMed  Google Scholar 

  128. Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. 2002;30(1):5–7.

    Article  CAS  PubMed  Google Scholar 

  129. Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. 1993;14(2):103–9.

    Article  CAS  PubMed  Google Scholar 

  130. Martin RB. Targeted bone remodeling involves BMU steering as well as activation. Bone. 2007;40(6):1574–80.

    Article  CAS  PubMed  Google Scholar 

  131. Verborgt O, Tatton NA, Majeska RJ, Schaffler MB. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? J Bone Min Res: Off J Am Soc Bone Min Res. 2002;17(5):907–14.

    Article  CAS  Google Scholar 

  132. Noble BS, Peet N, Stevens HY, Brabbs A, Mosley JR, Reilly GC, 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(4):C934–43.

    Article  CAS  PubMed  Google Scholar 

  133. Mann V, Huber C, Kogianni G, Jones D, Noble B. The influence of mechanical stimulation on osteocyte apoptosis and bone viability in human trabecular bone. J Musculoskelet Neuronal Interact. 2006;6(4):408–17.

    CAS  PubMed  Google Scholar 

  134. Kennedy OD, Herman BC, Laudier DM, Majeska RJ, Sun HB, Schaffler MB. Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. Bone. 2012;50(5):1115–22.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007;5(6):464–75.

    Article  CAS  PubMed  Google Scholar 

  136. Van Wesenbeeck L, Odgren PR, MacKay CA, D'Angelo M, Safadi FF, Popoff SN, et al. The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification. Proc Natl Acad Sci U S A. 2002;99(22):14303–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Wiktor-Jedrzejczak W, Bartocci A, Ferrante AW Jr, Ahmed-Ansari A, Sell KW, Pollard JW, et al. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci U S A. 1990;87(12):4828–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Marks SC Jr. Morphological evidence of reduced bone resorption in osteopetrotic (op) mice. Am J Anat. 1982;163(2):157–67.

    Article  PubMed  Google Scholar 

  139. Arai F, Miyamoto T, Ohneda O, Inada T, Sudo T, Brasel K, et al. Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med. 1999;190(12):1741–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Malone JD, Teitelbaum SL, Griffin GL, Senior RM, Kahn AJ. Recruitment of osteoclast precursors by purified bone matrix constituents. J Cell Biol. 1982;92(1):227–30.

    Article  CAS  PubMed  Google Scholar 

  141. Henriksen K, Leeming DJ, Byrjalsen I, Nielsen RH, Sorensen MG, Dziegiel MH, et al. Osteoclasts prefer aged bone. Osteoporos Int. 2007;18(6):751–9.

    Article  CAS  PubMed  Google Scholar 

  142. Yu X, Huang Y, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 (SDF-1) recruits osteoclast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration. J Bone Min Res: Off J Am Soc Bone Min Res. 2003;18(8):1404–18.

    Article  CAS  Google Scholar 

  143. Onan D, Allan EH, Quinn JM, Gooi JH, Pompolo S, Sims NA, et al. The chemokine Cxcl1 is a novel target gene of parathyroid hormone (PTH)/PTH-related protein in committed osteoblasts. Endocrinology. 2009;150(5):2244–53.

    Article  CAS  PubMed  Google Scholar 

  144. Zhu JF, Valente AJ, Lorenzo JA, Carnes D, Graves DT. Expression of monocyte chemoattractant protein 1 in human osteoblastic cells stimulated by proinflammatory mediators. J Bone Miner Res. 1994;9(7):1123–30.

    Article  CAS  PubMed  Google Scholar 

  145. Yu X, Huang Y, Collin-Osdoby P, Osdoby P. CCR1 chemokines promote the chemotactic recruitment, RANKL development, and motility of osteoclasts and are induced by inflammatory cytokines in osteoblasts. J Bone Min Res: Off J Am Soc Bone Min Res. 2004;19(12):2065–77.

    Article  CAS  Google Scholar 

  146. Li X, Qin L, Bergenstock M, Bevelock LM, Novack DV, Partridge NC. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. J Biol Chem. 2007;282(45):33098–106.

    Article  CAS  PubMed  Google Scholar 

  147. Ross FP, Teitelbaum SL. alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol Rev. 2005;208:88–105.

    Article  CAS  PubMed  Google Scholar 

  148. Malaval L, Wade-Gueye NM, Boudiffa M, Fei J, Zirngibl R, Chen F, et al. Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis. J Exp Med. 2008;205(5):1145–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Ihara H, Denhardt DT, Furuya K, Yamashita T, Muguruma Y, Tsuji K, et al. Parathyroid hormone-induced bone resorption does not occur in the absence of osteopontin. J Biol Chem. 2001;276(16):13065–71.

    Article  CAS  PubMed  Google Scholar 

  150. Chellaiah MA, Kizer N, Biswas R, Alvarez U, Strauss-Schoenberger J, Rifas L, et al. Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell. 2003;14(1):173–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Nethergate, Dundee, UK

    Christina Vrahnas

  2. Bone Cell Biology & Disease Unit, St. Vincent’s Institute of Medical Research, Fitzroy, VIC, Australia

    Natalie A. Sims

Authors
  1. Christina Vrahnas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalie A. Sims
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Natalie A. Sims .

Editor information

Editors and Affiliations

  1. Massachusetts General Hospital, Boston, MA, USA

    Benjamin Z. Leder

  2. Massachusetts General Hospital, Boston, MA, USA

    Marc N. Wein

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vrahnas, C., Sims, N.A. (2020). Basic Aspects of Osteoblast Function. In: Leder, B., Wein, M. (eds) Osteoporosis. Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-69287-6_1

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-319-69286-9

  • Online ISBN: 978-3-319-69287-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation