Osteoclasts-Key Players in Skeletal Health and Disease

Overview

Journal Microbiol Spectr

Specialty Microbiology

Date 2016 Jun 24

PMID 27337470

Citations 34

Authors

Deborah Veis Novack

Gabriel Mbalaviele

Affiliations

Soon will be listed here.

Abstract

The differentiation of osteoclasts (OCs) from early myeloid progenitors is a tightly regulated process that is modulated by a variety of mediators present in the bone microenvironment. Once generated, the function of mature OCs depends on cytoskeletal features controlled by an αvβ3-containing complex at the bone-apposed membrane and the secretion of protons and acid-protease cathepsin K. OCs also have important interactions with other cells in the bone microenvironment, including osteoblasts and immune cells. Dysregulation of OC differentiation and/or function can cause bone pathology. In fact, many components of OC differentiation and activation have been targeted therapeutically with great success. However, questions remain about the identity and plasticity of OC precursors and the interplay between essential networks that control OC fate. In this review, we summarize the key principles of OC biology and highlight recently uncovered mechanisms regulating OC development and function in homeostatic and disease states.

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References

Martin-Millan M, Almeida M, Ambrogini E, Han L, Zhao H, Weinstein R . The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol. 2010; 24(2):323-34. PMC: 2817608. DOI: 10.1210/me.2009-0354. View

Tawara K, Oxford J, Jorcyk C . Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies. Cancer Manag Res. 2011; 3:177-89. PMC: 3101113. DOI: 10.2147/CMR.S18101. View

Franceschi C, Campisi J . Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014; 69 Suppl 1:S4-9. DOI: 10.1093/gerona/glu057. View

Hughes A, Ralston S, Marken J, Bell C, MacPherson H, Wallace R . Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. Nat Genet. 1999; 24(1):45-8. DOI: 10.1038/71667. View

Vermeire K, Heremans H, Vandeputte M, Huang S, Billiau A, Matthys P . Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice. J Immunol. 1997; 158(11):5507-13. View

Otero K, Turnbull I, Poliani P, Vermi W, Cerutti E, Aoshi T . Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin. Nat Immunol. 2009; 10(7):734-43. PMC: 4004764. DOI: 10.1038/ni.1744. View

Mocsai A, Humphrey M, Van Ziffle J, Hu Y, Burghardt A, Spusta S . The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci U S A. 2004; 101(16):6158-63. PMC: 395939. DOI: 10.1073/pnas.0401602101. View

Mao D, Epple H, Uthgenannt B, Novack D, Faccio R . PLCgamma2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2. J Clin Invest. 2006; 116(11):2869-79. PMC: 1616195. DOI: 10.1172/JCI28775. View

Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M . Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med. 1997; 186(4):489-95. PMC: 2199029. DOI: 10.1084/jem.186.4.489. View

10.

Hurchla M, Garcia-Gomez A, Hornick M, Ocio E, Li A, Blanco J . The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia. 2012; 27(2):430-40. PMC: 3771507. DOI: 10.1038/leu.2012.183. View

11.

Hoff A, Catala-Lehnen P, Thomas P, Priemel M, Rueger J, Nasonkin I . Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. J Clin Invest. 2002; 110(12):1849-57. PMC: 151647. DOI: 10.1172/JCI14218. View

12.

Cauley J . Estrogen and bone health in men and women. Steroids. 2015; 99(Pt A):11-5. DOI: 10.1016/j.steroids.2014.12.010. View

13.

Mohammad K, Chen C, Balooch G, Stebbins E, McKenna C, Davis H . Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone. PLoS One. 2009; 4(4):e5275. PMC: 2666804. DOI: 10.1371/journal.pone.0005275. View

14.

Hayman A, Jones S, Boyde A, Foster D, Colledge W, Carlton M . Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis. Development. 1996; 122(10):3151-62. DOI: 10.1242/dev.122.10.3151. View

15.

Kong Y, Yoshida H, Sarosi I, Tan H, Timms E, Capparelli C . OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717):315-23. DOI: 10.1038/16852. View

16.

Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H . Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002; 3(6):889-901. DOI: 10.1016/s1534-5807(02)00369-6. View

17.

Bucay N, Sarosi I, Dunstan C, Morony S, Tarpley J, Capparelli C . osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998; 12(9):1260-8. PMC: 316769. DOI: 10.1101/gad.12.9.1260. View

18.

Koca S, Etem E, Isik B, Yuce H, Ozgen M, Dag M . Prevalence and significance of MEFV gene mutations in a cohort of patients with rheumatoid arthritis. Joint Bone Spine. 2009; 77(1):32-5. DOI: 10.1016/j.jbspin.2009.08.006. View

19.

Kiesel J, Buchwald Z, Aurora R . Cross-presentation by osteoclasts induces FoxP3 in CD8+ T cells. J Immunol. 2009; 182(9):5477-87. DOI: 10.4049/jimmunol.0803897. View

20.

Khachigian L . Collagen antibody-induced arthritis. Nat Protoc. 2007; 1(5):2512-6. DOI: 10.1038/nprot.2006.393. View