Regulation of Bone Resorption by Osteoclasts- an Overview
Main Article Content
Abstract
Osteoporosis is related to estrogen deficiency and aging. Bone loss can also occur as a result of inflammation-associated diseases such as rheumatoid arthritis and periodontitis, which share several pathologic features with osteoporosis. Estrogen deficiency is associated with increased osteoclast activation, decreased osteoblast function, and increased inflammatory bone-resorbing cytokines (e.g., interleukin-1, -6, and tumor necrosis factor –α). The differentiation of osteoclasts is regulated by the cytokines macrophage colony-stimulating factor, RANK ligand, and osteoprotegerin secreted by osteoblasts. Bone resorption is the unique function of osteoclasts. Podosomes are essential features of osteoclast migration. Podosomes are F-actin rich structures joined radially by actin fibers called F-actin cloud. Upon attachment to the bone surface, osteoclasts reorganize their cytoskeleton to form sealing zones. Sealing zone formation is required for efficient bone resorption to occur by osteoclasts. Integrin αvβ3 and TNF-alpha mediated signaling mechanisms regulate the assembly/disassembly of podosomes during migration and the organization of sealing zones during bone resorption. A brief description is provided on these aspects in this review.
Article Details
How to Cite
CHELLAIAH, Meenakshi A..
Regulation of Bone Resorption by Osteoclasts- an Overview.
Medical Research Archives, [S.l.], v. 8, n. 9, sep. 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2227>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v8i9.2227.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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2) Boyce BF, Li P, Yao Z et al. TNF-alpha and pathologic bone resorption. Keio J Med 2005;54:127-131.
3) Roggia C, Tamone C, Cenci S, Pacifici R, Isaia GC. Role of TNF-alpha producing T-cells in bone loss induced by estrogen deficiency. Minerva Med 2004;95:125-132.
4) Charatcharoenwitthaya N, Khosla S, Atkinson EJ, McCready LK, Riggs BL. Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women. J Bone Miner Res 2007;22:724-729.
5) Kanehisa J, Yamanaka T, Doi S et al. A band of F-actin containing podosomes is involved in bone resorption by osteoclasts. Bone 1990;11:287-293.
6) Akisaka T, Yoshida H, Inoue S, Shimizu K. Organization of cytoskeletal F-actin, G-actin, and gelsolin in the adhesion structures in cultured osteoclast. J Bone Miner Res 2001;16:1248-1255.
7) Pfaff M, Jurdic P. Podosomes in osteoclast-like cells: structural analysis and cooperative roles of paxillin, proline-rich tyrosine kinase 2 (Pyk2) and integrin alphaVbeta3. J Cell Sci 2001;114:2775-2786.
8) Marchisio PC, Cirillo D, Naldini L, Primavera MV, Teti A, Zambonin-Zallone A. Cell-substratum interaction of cultured avian osteoclasts is mediated by specific adhesion structures. J Cell Biol 1984;99:1696-1705.
9) Zhang D, Murakami H, Udagawa N et al. The small GTP-binding protein Rho is involved in osteoclastic bone resorption by regulating podosome formation. J Bone Miner Res 1994;9:S131.
10) Chellaiah M, Fitzgerald C, Alvarez U, Hruska K. C-src is required for stimulation of gelsolin associated PI3-K. J Biol Chem 1998;273:11908-11916.
11) Chellaiah M, Kizer N, Silva M, Alvarez U, Kwiatkowski D, Hruska KA. Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength. J Cell Biol 2000;148:665-678.
12) Chellaiah M, Soga N, Swanson S et al. Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J Biol Chem 2000;275:11993-12002.
13) Nakamura I, Pilkington MF, Lakkakorpi PT et al. Role of alpha(v)beta(3) integrin in osteoclast migration and formation of the sealing zone. J Cell Sci 1999;112 ( Pt 22):3985-3993.
14) Duong LT, Lakkakorpi PT, Nakamura I, Machwate M, Nagy RM, Rodan GA. PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of avb3 integrin, and phosphorylated by Src kinase. J Clin Invest 1998;102:881-892.
15) Wang Q, Xie Y, Du QS et al. Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin. J Cell Biol 2003;160:565-575.
16) Hiroi-Furuya E, Kameda T, Hiura K et al. Etidronate (EHDP) inhibits osteoclastic-bone resorption, promotes apoptosis and disrupts actin rings in isolate-mature osteoclasts. Calcif Tissue Int 1999;64:219-223.
17) Lakkakorpi PT, Nakamura I, Young M, Lipfert L, Rodan GA, Duong LT. Abnormal localization and hyperclustering of (alpha)(V)(beta)(3) integrins and associated proteins in Src-deficient or tyrphostin A9-treated osteoclasts. J Cell Sci 2001;114:149-160.
18) Hurst IR, Zuo J, Jiang J, Holliday LS. Actin-related protein 2/3 complex is required for actin ring formation. J Bone Miner Res 2004;19:499-506.
19) Ma T, Samanna V, Chellaiah MA. Dramatic inhibition of osteoclast sealing ring formation and bone resorption in vitro by a WASP-peptide containing pTyr294 amino acid. J Mol Signal 2008;3:4.
20) Chellaiah MA, Moorer MC, Majumdar S et al. L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction. Bone Res 2020;8:3.
21) Lakkakorpi P, Tuukkanen J, Hentunen T, Jarvelin K, Vaananen K. Organization of osteoclast microfilaments during the attachment to bone surface in vitro. J Bone Miner Res 1989;4:817-825.
22) Lakkakorpi PT, Vaananen HK. Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro. J Bone Miner Res 1991;6:817-826.
23) Teti A, Marchisio PC, Zambonin-Zallone A. Clear zone in osteoclast function: role of podosomes in regulation of bone-resorbing activity (Review). Amer J Physiol 1991;261:C1-C7.
24) Jurdic P, Saltel F, Chabadel A, Destaing O. Podosome and sealing zone: specificity of the osteoclast model. Eur J Cell Biol 2006;85:195-202.
25) Saltel F, Destaing O, Bard F, Eichert D, Jurdic P. Apatite-mediated actin dynamics in resorbing osteoclasts. Mol Biol Cell 2004;15:5231-5241.
26) Taylor ML, Boyde A, Jones SJ. The effect of fluoride on the patterns of adherence of osteoclasts cultured on and resorbing dentine: a 3-D assessment of vinculin-labelled cells using confocal optical microscopy. Anat Embryol (Berl) 1989;180:427-435.
27) McHugh KP, Hodivala-Dilke K, Zheng M-H et al. Mice lacking b3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest 2000;105:433-440.
28) Feng X, Novack DV, Faccio R et al. A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast function. J Clin Invest 2001;107:1137-1144.
29) Murakami H, Takahashi N, Sasaki T et al. A possible mechanism of the specific action of bisphosphonates on osteoclasts: Tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone 1995;17:137-144.
30) Zhang D, Udagawa N, Nakamura I et al. The small GTP-binding protein, rho p21, is involved in bone resorption by regulating cytoskeletal organization in osteoclasts. Journal of Cell Science 1995;108:2285-2292.
31) Duong LT, Rodan GA. Integrin-mediated signaling in the regulation of osteoclast adhesion and activation. Front Biosci 1998;3:d757-d768.
32) Izawa T, Zou W, Chappel JC, Ashley JW, Feng X, Teitelbaum SL. c-Src links a RANK/alphavbeta3 integrin complex to the osteoclast cytoskeleton. Mol Cell Biol 2012;32:2943-2953.
33) Faccio R, Teitelbaum SL, Fujikawa K et al. Vav3 regulates osteoclast function and bone mass. Nat Med 2005;11:284-290.
34) Chellaiah MA, Schaller MD. Activation of Src kinase by protein-tyrosine phosphatase-PEST in osteoclasts: comparative analysis of the effects of bisphosphonate and protein-tyrosine phosphatase inhibitor on Src activation in vitro. J Cell Physiol 2009;220:382-393.
35) Chellaiah MA. Regulation of actin ring formation by rho GTPases in osteoclasts. J Biol Chem 2005;280:32930-32943.
36) Gupta A, Lee BS, Khadeer MA et al. Leupaxin is a critical adaptor protein in the adhesion zone of the osteoclast. J Bone Miner Res 2003;18:669-685.
37) Miyazaki T, Tanaka S, Sanjay A, Baron R. The role of c-Src kinase in the regulation of osteoclast function. Mod Rheumatol 2006;16:68-74.
38) Duong LT, Lakkakorpi PT, Nakamura I, Machwate M, Nagy RM, Rodan GA. PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and phosphorylated by src kinase. J Clin Invest 1998;102:881-892.
39) Chellaiah MA, Biswas RS, Yuen D, Alvarez UM, Hruska KA. Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2-containing signaling proteins with gelsolin. J Biol Chem 2001;276:47434-47444.
40) Baron R. Molecular mechanisms of bone resorption. An update. Acta Orthop Scand Suppl 1995;266:66-70.
41) Teitelbaum SL. The osteoclast and its unique cytoskeleton. Ann N Y Acad Sci 2011;1240:14-17.
42) Chellaiah MA, Kuppuswamy D, Lasky L, Linder S. Phosphorylation of a Wiscott-Aldrich syndrome protein-associated signal complex is critical in osteoclast bone resorption. J Biol Chem 2007;282:10104-10116.
43) Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 1991;64:693-702.
44) Sanjay A, Houghton A, Neff L et al. Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility. J Cell Biol 2001;152:181-195.
45) Ory S, Munari-Silem Y, Fort P, Jurdic P. Rho and Rac exert antagonistic functions on spreading of macrophage-derived multinucleated cells and are not required for actin fiber formation. J Cell Sci 2000;113 ( Pt 7):1177-1188.
46) Chellaiah MA. Regulation of podosomes by integrin alphavbeta3 and Rho GTPase-facilitated phosphoinositide signaling. Eur J Cell Biol 2006;85:311-317.
47) McMichael BK, Scherer KF, Franklin NC, Lee BS. The RhoGAP activity of myosin IXB is critical for osteoclast podosome patterning, motility, and resorptive capacity. PLoS ONE 2014;9:e87402.
48) Teitelbaum SL. Osteoclasts and integrins. Ann N Y Acad Sci 2006;1068:95-99.
49) Novack DV, Faccio R. Osteoclast motility: putting the brakes on bone resorption. Ageing Res Rev 2011;10:54-61.
50) Calle Y, Jones GE, Jagger C et al. WASp deficiency in mice results in failure to form osteoclast sealing zones and defects in bone resorption. Blood 2004.
51) Lee J, Park C, Kim HJ et al. Stimulation of osteoclast migration and bone resorption by C-C chemokine ligands 19 and 21. Exp Mol Med 2017;49:e358.
52) Tehrani S, Faccio R, Chandrasekar I, Ross FP, Cooper JA. Cortactin has an essential and specific role in osteoclast actin assembly. Mol Biol Cell 2006;17:2882-2895.
53) Iwatake M, Nishishita K, Okamoto K, Tsukuba T. The Rho-specific guanine nucleotide exchange factor Plekhg5 modulates cell polarity, adhesion, migration, and podosome organization in macrophages and osteoclasts. Exp Cell Res 2017;359:415-430.
54) Rogers MJ. New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des 2003;9:2643-2658.
55) Destaing O, Saltel F, Geminard J-C, Jurdic P, Bard FA. Podosomes display actin turn over and dynamic self organization in osteoclasts expressing actin-green fluorescent protein. Actin-GFP in osteoclasts. Molecular Biology of the Cell 14[2003], 407-416. 2003.
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