Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical Oral Investigations
Published in: Clinical Oral Investigations 4/2009

01-12-2009 | Review

The molecular mechanism behind bone remodelling: a review

Authors: Peter Proff, Piero Römer

Published in: Clinical Oral Investigations | Issue 4/2009

Login to get access

Abstract

Bone is a connective tissue and guarantees protection and support of organ function. Contrary to the common view, bone is a dynamic tissue that constantly undergoes turnover in order to maintain stability and integrity. In this process called bone turnover or bone remodelling, two effector cell types are involved. Osteoclasts, specialised for bone resorption, and osteoblasts, responsible for bone formation, are key players in bone turnover. In the past decade, a lot of information about signal pathways, osteoblast–osteoclast communication and osteoclast activation concerning bone remodelling has arisen. In this publication, we aim to review molecular and biochemical insights with respect to the bone remodelling process. The bone remodelling process is of fundamental importance for craniofacial growth, orthodontic tooth movement and regenerative dentistry.
Literature
1.
Arnett TR, Lindsay R, Kilb JM, Moonga BS, Spowage M, Dempster DW (1996) Selective toxic effects of tamoxifen on osteoclasts: comparison with the effects of oestrogen. J Endocrinol 149:503–508CrossRefPubMed
2.
Balemans W, Van Hul W (2002) Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Review. Dev Biol 250:231–250PubMed
3.
Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ (2001) Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 28:465–473CrossRefPubMed
4.
Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, MacDougald OA (2005) Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA 102:3324–3329CrossRefPubMed
5.
Bodine PV, Komm BS (2006) Wnt signaling and osteoblastogenesis. Review. Rev Endocr Metab Disord 7:33–39CrossRefPubMed
6.
Bonewald LF (2007) Osteocytes as dynamic multifunctional cells. Review. Ann N Y Acad Sci 1116:281–290CrossRefPubMed
7.
Boyce BF, Yao Z, Zhang Q, Guo R, Lu Y, Schwarz EM, Xing L (2007) New roles for osteoclasts in bone. Review. Ann N Y Acad Sci 1116:245–254CrossRefPubMed
8.
9.
Chambers TJ, Moore A (1983) The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. J Clin Endocrinol Metab 57:819–824CrossRefPubMed
10.
Datta HK, Ng WF, Walker JA, Tuck SP, Varanasi SS (2008) The cell biology of bone metabolism. J Clin Pathol 61:577–587CrossRefPubMed
11.
Delaissé JM, Engsig MT, Everts V, del Carmen Ovejero M, Ferreras M, Lund L, Vu TH, Werb Z, Winding B, Lochter A, Karsdal MA, Troen T, Kirkegaard T, Lenhard T, Heegaard AM, Neff L, Baron R, Foged NT (2000) Proteinases in bone resorption: obvious and less obvious roles. Clin Chim Acta 291:223–234CrossRefPubMed
12.
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 (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424CrossRefPubMed
13.
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754CrossRefPubMed
14.
Duong LT, Lakkakorpi P, Nakamura I, Rodan GA (2000) Integrins and signaling in osteoclast function. Matrix Biol 19:97–105CrossRefPubMed
15.
Felix R, Cecchini MG, Fleisch H (1990) Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology 127:2592–2604CrossRefPubMed
16.
Fermor B, Skerry TM (1995) PTH/PTHrP receptor expression on osteoblasts and osteocytes but not resorbing bone surfaces in growing rats. J Bone Miner Res 10:1935–1943PubMedCrossRef
17.
Franz-Odendaal TA, Hall BK, Witten PE (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235:176–190CrossRefPubMed
18.
Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 280:33132–33140CrossRefPubMed
19.
Glass DA 2nd, Karsenty G (2007) In vivo analysis of Wnt signaling in bone. Endocrinology 148:2630–2634CrossRefPubMed
20.
Glantschnig H, Fisher JE, Wesolowski G, Rodan GA, Reszka AA (2003) M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase. Cell Death Differ 10:1165–1177CrossRefPubMed
21.
Gong Y, Slee RB, Fukai N et al (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523CrossRefPubMed
22.
Graves DT, Alsulaimani F, Ding Y, Marks SC Jr (2002) Developmentally regulated monocyte recruitment and bone resorption are modulated by functional deletion of the monocytic chemoattractant protein-1 gene. Bone 31:282–287CrossRefPubMed
23.
24.
Harada H, Tagashira S, Fujiwara M, Ogawa S, Katsumata T, Yamaguchi A, Komori T, Nakatsuka M (1999) Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem 274:6972–6978CrossRefPubMed
25.
26.
Hofbauer LC, Heufelder AE (2001) Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243–253CrossRefPubMed
27.
28.
Horwood NJ, Elliott J, Martin TJ, Gillespie MT (1998) Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139:4743–4766CrossRefPubMed
29.
Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M, Nakamaru Y, Hiroi E, Hiura K, Kameda A, Yang NN, Hakeda Y, Kumegawa M (1997) Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med 186:489–495CrossRefPubMed
30.
Kassem M, Abdallah BM, Saeed H (2008) Osteoblastic cells: differentiation and trans-differentiation. Arch Biochem Biophys 473:183–187CrossRefPubMed
31.
Katagiri T, Takahashi N (2002) Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 8:147–159CrossRefPubMed
32.
Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T (1994) Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 127:1755–1766CrossRefPubMed
33.
Kodama H, Yamasaki A, Nose M, Niida S, Ohgame Y, Abe M, Kumegawa M, Suda T (1991) Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor. J Exp Med 173:269–272CrossRefPubMed
34.
Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M et al (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764CrossRefPubMed
35.
Kostenuik PJ (2005) Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 5:618–625CrossRefPubMed
36.
Kretzschmar M, Liu F, Hata A, Doody J, Massagué J (1997) The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev 11:984–995CrossRefPubMed
37.
Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209CrossRefPubMed
38.
Kurihara N, Suda T, Miura Y, Nakauchi H, Kodama H, Hiura K, Hakeda Y, Kumegawa M (1989) Generation of osteoclasts from isolated hematopoietic progenitor cells. Blood 74:1295–1302PubMed
39.
Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561CrossRefPubMed
40.
41.
Li X, Qin L, Bergenstock M, Bevelock LM, Novack DV, Partridge NC (2007) Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. J Biol Chem 282:33098–33106CrossRefPubMed
42.
Logar DB, Komadina R, Prezelj J, Ostanek B, Trost Z, Marc J (2007) Expression of bone resorption genes in osteoarthritis and in osteoporosis. J Bone Miner Metab 25:219–225CrossRefPubMed
43.
Lorget F, Kamel S, Mentaverri R, Wattel A, Naassila M, Maamer M, Brazier M (2000) High extracellular calcium concentrations directly stimulate osteoclast apoptosis. Biochem Biophys Res Commun 268:899–903CrossRefPubMed
44.
Malgaroli A, Meldolesi J, Zallone AZ, Teti A (1989) Control of cytosolic free calcium in rat and chicken osteoclasts. The role of extracellular calcium and calcitonin. J Biol Chem 264:14342–14347PubMed
45.
Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C (2002) Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417:664–667CrossRefPubMed
46.
47.
Miyauchi A, Alvarez J, Greenfield EM, Teti A, Grano M, Colucci S, Zambonin-Zallone A, Ross FP, Teitelbaum SL, Cheresh D et al (1991) Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. J Biol Chem 266:20369–20374PubMed
48.
Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng J, Behringer R, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29CrossRefPubMed
49.
Nakashima K, de Crombrugghe B (2003) Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet 19:458–466CrossRefPubMed
50.
51.
O'Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, Robling AG, Bouxsein M, Schipani E, Turner CH, Jilka RL, Weinstein RS, Manolagas SC, Bellido T (2008) Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS ONE 3:e2942CrossRefPubMed
52.
Odgren PR, Kim N, MacKay CA, Mason-Savas A, Choi Y, Marks SC Jr (2003) The role of RANKL (TRANCE/TNFSF11), a tumor necrosis factor family member, in skeletal development: effects of gene knockout and transgenic rescue. Connect Tissue Res 44:264–271CrossRefPubMed
53.
Phimphilai M, Zhao Z, Boules H, Roca H, Franceschi RT (2006) BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J Bone Miner Res 21:637–646CrossRefPubMed
54.
Piters E, Boudin E, Van Hul W (2008) Wnt signaling: a win for bone. Arch Biochem Biophys 473:112–116CrossRefPubMed
55.
Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J (2005) Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 19:1842–1844PubMed
56.
Ramasamy I (2006) Recent advances in physiological calcium homeostasis. Clin Chem Lab Med 44:237–273CrossRefPubMed
57.
58.
Saftig P, Hunziker E, Everts V, Jones S, Boyde A, Wehmeyer O, Suter A, von Figura K (2000) Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice. Adv Exp Med Biol 477:293–303CrossRefPubMed
59.
Silver IA, Murrills RJ, Etherington DJ (1988) Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res 175:266–276CrossRefPubMed
60.
Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy 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 (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319CrossRefPubMed
61.
Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357CrossRefPubMed
62.
Takahashi N, Udagawa N, Suda T (1999) A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun 256:449–455CrossRefPubMed
63.
Takahashi N, Akatsu T, Udagawa N, Sasaki T, Yamaguchi A, Moseley JM, Martin TJ, Suda T (1988) Osteoblastic cells are involved in osteoclast formation. Endocrinology 123:2600–2602CrossRefPubMed
64.
65.
Theill LE, Boyle WJ, Penninger JM (2002) RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 20:795–823CrossRefPubMed
66.
67.
68.
van Bezooijen R, Dijke P, Papapoulos S, Löwik CGM (2005) Sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev 16:319–327CrossRefPubMed
69.
Väänänen HK, Laitala-Leinonen T (2008) Osteoclast lineage and function. Arch Biochem Biophys 473:132–138CrossRefPubMed
70.
Wada T, Nakashima T, Hiroshi N, Penninger JM (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12:17–25CrossRefPubMed
71.
Wennberg C, Hessle L, Lundberg P, Mauro S, Narisawa S, Lerner UH, Millán JL (2000) Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice. J Bone Miner Res 15:1879–1888CrossRefPubMed
72.
Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95:3597–3602CrossRefPubMed
73.
Yavropoulou MP, Yovos JG (2007) The role of the Wnt signaling pathway in osteoblast commitment and differentiation. Hormones (Athens) 6:279–294
74.
Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD, Nishikawa S (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345:442–444CrossRefPubMed
Metadata
Title
The molecular mechanism behind bone remodelling: a review
Authors
Peter Proff
Piero Römer
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
Clinical Oral Investigations / Issue 4/2009
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-009-0268-2

Other articles of this Issue 4/2009

Clinical Oral Investigations 4/2009 Go to the issue

Original Article

Calibration of radiographs by a reference metal ball affects preoperative selection of implant size

Original Article

Dimensional changes of periodontal soft tissues after intrasulcular incision

Letter to the Editor

“Fatigue” having a role in the pathogenesis of osteonecrosis of the jaws

Original Article

Investigations on mechanical behaviour of dental composites

Erratum

Investigations on mechanical behaviour of dental composites

Original Article

Marginal adaptation of three self-adhesive resin cements vs. a well-tried adhesive luting agent