Journal List > J Korean Soc Endocrinol > v.20(6) > 1063827

Shin and Cho: Bone Remodeling and Mineralization

Figures and Tables

Fig. 1
Bone remodeling is accomplished by cycles involving the resorption of old bone by osteoclasts and the subsequent formation of new bone by osteoblasts.
Fig. 2
Relative proportions of cortical (compact) and trabecular (cancellous) bone in different parts of the skeleton.
Fig. 3
Osteoblast/stromal cell and osteoclast coupling mediated through RANKL/RANK interactions.
Fig. 4
Factors that modulate the differentiation and function of osteoblast and osteoclast.
Fig. 5
Growth factor concept of coupling.
Fig. 6
Effects of antiresorptive agent on remodeling space and mineralization in the basic multicellular units.
Fig. 7
Primary and secondary mineralization phase. The secondary mineralization period is defined as the time required for bone to mineralize from 70% to 95% of the theoretical maximum ash fraction.
Table 1
Characteristics of Collagen-Related Genes and Proteins found in Bone matrix (from ref. 42)
Table 2
Gene and Proteins Characteristics of Serum proteins found in Bone matrix (from ref. 42)
Table 3
Gene and Proteins Characteristics of Glycoproteins in bone matrix (from ref. 42)
Table 4
Gene and Proteins Characteristics of Glycosaminoglycan-Containing Molecules, Leucine Rich Repeat Proteins(LPRs) and Hyaluronan (from ref. 42)
Table 5
Gene and Proteins Characteristics of SIBLINGs (Small Integrin-Binding Ligands, N-Glycosylated Proteins) (from ref. 42)
Table 6
Gene and Proteins Characteristics of Other RGD-Containing Gycoproteins (from ref. 42)
Table 7
Gene and Proteins Characteristics of Gamma-Carboxy Glutamic Acid-Contaning Proteins in Bone Matrix (from ref. 42)
Table 8
Effects of Bone Matrix Proteins on Mineralization in VITRO (from ref. 42)
Table 9
Cytokines produced in bone microenvironment with major effects on Osteoblasts and Osteoclasts(from ref. 42)


1. Rossert J, Crombrugghe B. Bilezikian J, Raisz L, Rodan G, editors. Type I collagen: Structure, synthesis and regulation. Principles of bone biology 1. 2002. San Diego,USA: Academic Press.
2. Gokhale J, Robey P, Boskey A. Marcus R, Feldman D, Kelsey A, editors. The biochemistry of bone. Osteoporosis 1. 2001. San Diego, USA: Academic Press;107–188.
3. Seibel MJ, Woitge HW. Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects. J Clin Densitom. 1999. 2:299–321.
4. Gorski JP. Is all bone the same? Distinctive distributions and properties of non-collagenous matrix proteins in lamellar vs. woven bone imply the existence of different underlying osteogenic mechanisms. Crit Rev Oral Biol Med. 1998. 9:201–223.
5. Glimcher MJ. Mechanism of calcification: role of collagen fibrils and collagen-phosphoprotein complexes in vitro and in vivo. Anat Rec. 1989. 224:139–153.
6. Anderson HC. Mineralization by matrix vesicles. Scan Electron Microsc. 1984. 953–964.
7. Termine JD, Belcourt AB, Conn KM, Kleinman HK. Mineral and collagen-binding proteins of fetal calf bone. J Biol Chem. 1981. 256:10403–10408.
8. Stubbs JT 3rd, Mintz KP, Eanes ED, Torchia DA, Fisher LW. Characterization of native and recombinant bone sialoprotein: delineation of the mineral-binding and cell adhesion domains and structural analysis of the RGD domain. J Bone Miner Res. 1997. 12:1210–1222.
9. Boskey AL. Osteopontin and related phosphorylated sialoproteins: effects on mineralization. Ann N Y Acad Sci. 1995. 760:249–256.
10. Frost H. Dynamics of bone remodeling. Bone Biodynamics. 1964. Boston, MA: Little and Brown;315.
11. Riggs BL, Wahner HW, Melton LJ 3rd, Richelson LS, Judd HL, Offord KP. Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause. J Clin Invest. 1986. 77:1487–1491.
12. Genant HK, Cann CE, Ettinger B, Gordan GS. Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting early bone loss after oophorectomy. Ann Intern Med. 1982. 97:699–705.
13. Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption--a hypothesis. Calcif Tissue Int. 1981. 33:349–351.
14. Howard GA, Bottemiller BL, Turner RT, Rader JI, Baylink DJ. Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism. Proc Natl Acad Sci U S A. 1981. 78:3204–3208.
15. Locklin RM, Khosla S, Turner RT, Riggs BL. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. J Cell Biochem. 2003. 89:180–190.
16. Enomoto H, Shiojiri S, Hoshi K, Furuichi T, Fukuyama R, Yoshida CA, Kanatani N, Nakamura R, Mizuno A, Zanma A, Yano K, Yasuda H, Higashio K, Takada K, Komori T. Induction of osteoclast differentiation by Runx2 through receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene. J Biol Chem. 2003. 278:23971–23977.
17. Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell. 2005. 122:803–815.
18. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005. 434:514–520.
19. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997. 89:309–319.
20. Akatsu T, Murakami T, Ono K, Nishikawa M, Tsuda E, Mochizuki SI, Fujise N, Higashio K, Motoyoshi K, Yamamoto M, Nagata N. Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. Bone. 1998. 23:495–498.
21. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998. 12:1260–1268.
22. Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun. 1998. 247:610–615.
23. Yamamoto M, Murakami T, Nishikawa M, Tsuda E, Mochizuki S, Higashio K, Akatsu T, Motoyoshi K, Nagata N. Hypocalcemic effect of osteoclastogenesis inhibitory factor/osteoprotegerin in the thyroparathyroidectomized rat. Endocrinology. 1998. 139:4012–4015.
24. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998. 93:165–176.
25. Lum L, Wong BR, Josien R, Becherer JD, Erdjument-Bromage H, Schlondorff J, Tempst P, Choi Y, Blobel CP. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J Biol Chem. 1999. 274:13613–13618.
26. Wong BR, Josien R, Choi Y. TRANCE is a TNF family member that regulates dendritic cell and osteoclast function. J Leukoc Biol. 1999. 65:715–724.
27. Kong YY, Boyle WJ, Penninger JM. Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development. Immunol Cell Biol. 1999. 77:188–193.
28. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999. 397:315–323.
29. Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle WJ. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A. 2000. 97:1566–1571.
30. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999. 13:2412–2424.
31. Noda M, Camilliere JJ. In vivo stimulation of bone formation by transforming growth factor-beta. Endocrinology. 1989. 124:2991–2994.
32. Filvaroff E, Erlebacher A, Ye J, Gitelman SE, Lotz J, Heillman M, Derynck R. Inhibition of TGF-beta receptor signaling in osteoblasts leads to decreased bone remodeling and increased trabecular bone mass. Development. 1999. 126:4267–4279.
33. Sabatini M, Boyce B, Aufdemorte T, Bonewald L, Mundy GR. Infusions of recombinant human interleukins 1 alpha and 1 beta cause hypercalcemia in normal mice. Proc Natl Acad Sci U S A. 1988. 85:5235–5239.
34. Pacifici R, Rifas L, McCracken R, Vered I, McMurtry C, Avioli LV, Peck WA. Ovarian steroid treatment blocks a postmenopausal increase in blood monocyte interleukin 1 release. Proc Natl Acad Sci U S A. 1989. 86:2398–2402.
35. Felix R, Cecchini MG, Fleisch H. Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology. 1990. 127:2592–2594.
36. Pfeilschifter J, Bonewald L, Mundy GR. Characterization of the latent transforming growth factor beta complex in bone. J Bone Miner Res. 1990. 5:49–58.
37. Canalis E, McCarthy T, Centrella M. Growth factors and the regulation of bone remodeling. J Clin Invest. 1988. 81:277–281.
38. Canalis E, Pash J, Gabbitas B, Rydziel S, Varghese S. Growth factors regulate the synthesis of insulin-like growth factor-I in bone cell cultures. Endocrinology. 1993. 133:33–38.
39. Krane SM. Identifying genes that regulate bone remodeling as potential therapeutic targets. J Exp Med. 2005. 201:841–843.
40. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh , Recker RR, Johnson ML. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002. 70:11–19.
41. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, HeegerS , Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001. 107:513–523.
42. Robey PG, Boskey AL. Favus MJ, editor. Extracellular matrix and biomineralization of bone. Primer on the metabolic bone diseases and disorders of mineral metabolism. 2003. Washington D.C.: American Society of Bone and Mineral Research;38–46.
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