Transcriptional Regulation of Bone and Joint Remodeling by NFAT

Overview

Journal Immunol Rev

Specialties Allergy & Immunology
General Surgery

Date 2010 Mar 3

PMID 20193006

Citations 57

Authors

Despina Sitara

Antonios O Aliprantis

Affiliations

Soon will be listed here.

Abstract

Osteoporosis and arthritis are highly prevalent diseases and a significant cause of morbidity and mortality worldwide. These diseases result from aberrant tissue remodeling leading to weak, fracture-prone bones or painful, dysfunctional joints. The nuclear factor of activated T cells (NFAT) transcription factor family controls diverse biologic processes in vertebrates. Here, we review the scientific evidence that links NFAT-regulated gene transcription to bone and joint pathology. A particular emphasis is placed on the role of NFATs in bone resorption and formation by osteoclasts and osteoblasts, respectively. In addition, emerging data that connect NFATs with cartilage biology, angiogenesis, nociception, and neurogenic inflammation are explored. The goal of this article is to highlight the importance of tissue remodeling in musculoskeletal disease and situate NFAT-driven cellular responses within this context to inspire future research endeavors.

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References

Goldring S . Bone and joint destruction in rheumatoid arthritis: what is really happening?. J Rheumatol Suppl. 2002; 65:44-8. View

Hogan P, Chen L, Nardone J, Rao A . Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003; 17(18):2205-32. DOI: 10.1101/gad.1102703. View

Shen Z, Crotti T, Flannery M, Matsuzaki K, Goldring S, McHugh K . A novel promoter regulates calcitonin receptor gene expression in human osteoclasts. Biochim Biophys Acta. 2007; 1769(11-12):659-67. DOI: 10.1016/j.bbaexp.2007.08.005. View

Boyle W, Simonet W, Lacey D . Osteoclast differentiation and activation. Nature. 2003; 423(6937):337-42. DOI: 10.1038/nature01658. View

Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F . Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med. 2002; 8(8):831-40. DOI: 10.1038/nm731. View

Ueki Y, Lin C, Senoo M, Ebihara T, Agata N, Onji M . Increased myeloid cell responses to M-CSF and RANKL cause bone loss and inflammation in SH3BP2 "cherubism" mice. Cell. 2007; 128(1):71-83. DOI: 10.1016/j.cell.2006.10.047. View

Schroeder T, Nair A, Staggs R, Lamblin A, Westendorf J . Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors. BMC Genomics. 2007; 8:362. PMC: 2147034. DOI: 10.1186/1471-2164-8-362. View

Ganea D, Gonzalez-Rey E, Delgado M . A novel mechanism for immunosuppression: from neuropeptides to regulatory T cells. J Neuroimmune Pharmacol. 2007; 1(4):400-9. DOI: 10.1007/s11481-006-9044-0. View

Otto F, Thornell A, Crompton T, Denzel A, Gilmour K, Rosewell I . Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 1997; 89(5):765-71. DOI: 10.1016/s0092-8674(00)80259-7. View

10.

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

11.

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

12.

Courtwright A, Siamakpour-Reihani S, Arbiser J, Banet N, Hilliard E, Fried L . Secreted frizzle-related protein 2 stimulates angiogenesis via a calcineurin/NFAT signaling pathway. Cancer Res. 2009; 69(11):4621-8. PMC: 2699405. DOI: 10.1158/0008-5472.CAN-08-3402. View

13.

Balcerzak M, Hamade E, Zhang L, Pikula S, Azzar G, Radisson J . The roles of annexins and alkaline phosphatase in mineralization process. Acta Biochim Pol. 2004; 50(4):1019-38. View

14.

Simonet W, Lacey D, Dunstan C, Kelley M, Chang M, Luthy R . Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89(2):309-19. DOI: 10.1016/s0092-8674(00)80209-3. View

15.

Pessler F, Dai L, Cron R, Schumacher H . NFAT transcription factors--new players in the pathogenesis of inflammatory arthropathies?. Autoimmun Rev. 2006; 5(2):106-10. DOI: 10.1016/j.autrev.2005.08.007. View

16.

Kitahara K, Kawai S . Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2007; 19(3):238-45. DOI: 10.1097/BOR.0b013e328099af80. View

17.

Sharaki O, El-Guiziry D, Abou-Zeid A, El-Noueam K, Helal A, Gaballah A . Clinical usefulness of basic fibroblast growth factor and E-selectin in patients with rheumatoid arthritis. Egypt J Immunol. 2006; 11(2):91-100. View

18.

Alper S . Molecular physiology of SLC4 anion exchangers. Exp Physiol. 2005; 91(1):153-61. DOI: 10.1113/expphysiol.2005.031765. View

19.

Walsh N, Crotti T, Goldring S, Gravallese E . Rheumatic diseases: the effects of inflammation on bone. Immunol Rev. 2005; 208:228-51. DOI: 10.1111/j.0105-2896.2005.00338.x. View

20.

Jinnin M, Medici D, Park L, Limaye N, Liu Y, Boscolo E . Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med. 2008; 14(11):1236-46. PMC: 2593632. DOI: 10.1038/nm.1877. View