Bone remodeling and homeostasis is an essential function that regulates skeletal integrity throughout adult life in higher vertebrates and mammals. The structural and metabolic integrity of bone is maintained through the dynamic process of bone remodeling that results from the coordinate action of bone resorption by osteoclasts and the formation of new bone by osteoblasts. Regulation of bone remodeling occurs through multiple mechanisms that ultimately converge on the interaction of osteoclasts or their precursors with osteoblasts and bone marrow stromal cells. Key factors supplied by the stromal environment are cytokines such as IL-1, IL-11, IL-17, CSF1 (Colony Stimulating Factor-1) and the TNF receptor ligand family, RANKL (Receptor Activator of NF-kappaB Ligand; also known as OPGL, TRANCE, ODF and TNFSF11) and its receptor RANK (TNFRSF11A). Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in Rheumatoid Arthritis or generalized bone loss (Ref.1 & 2). References 1.Bone remodelling at a glance. Crockett JC, Rogers MJ, Coxon FP, Hocking LJ, Helfrich MH. J Cell Sci. 2011 Apr 1;124(Pt 7):991-8. 2.Osteoblast physiology in normal and pathological conditions. Neve A, Corrado A, Cantatore FP. Cell Tissue Res. 2011 Feb;343(2):289-302. Epub 2010 Dec 1. Dougall WC. Clin Cancer Res. 2012 Jan 15;18(2):326-35. Epub 2011 Oct 26. Mellis DJ, Itzstein C, Helfrich MH, Crockett JC. J Endocrinol. 2011 Nov;211(2):131-43. doi: 10.1530/JOE-11-0212. Epub 2011 Sep 8. 5.RANK(L) as a key target for controlling bone loss. Leibbrandt A, Penninger JM. Adv Exp Med Biol. 2009;647:130-45. 6.RANK/RANKL: regulators of immune responses and bone physiology. Leibbrandt A, Penninger JM. Ann N Y Acad Sci. 2008 Nov;1143:123-50.
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