%0 Journal Article
%T The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis
%A M. Neale Weitzmann
%J Scientifica
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/125705
%X Although it has long been recognized that inflammation, a consequence of immune-driven processes, significantly impacts bone turnover, the degree of centralization of skeletal and immune functions has begun to be dissected only recently. It is now recognized that formation of osteoclasts, the bone resorbing cells of the body, is centered on the key osteoclastogenic cytokine, receptor activator of NF-¦ĘB ligand (RANKL). Although numerous inflammatory cytokines are now recognized to promote osteoclast formation and skeletal degradation, with just a few exceptions, RANKL is now considered to be the final downstream effector cytokine that drives osteoclastogenesis and regulates osteoclastic bone resorption. The biological activity of RANKL is moderated by its physiological decoy receptor, osteoprotegerin (OPG). New discoveries concerning the sources and regulation of RANKL and OPG in physiological bone turnover as well as under pathological (osteoporotic) conditions continue to be made, opening a window to the complex regulatory processes that control skeletal integrity and the depth of integration of the skeleton within the immune response. This paper will examine the interconnection between bone turnover and the immune system and the implications thereof for physiological and pathological bone turnover. 1. Introduction Mineralized bone consists of a protein matrix comprising predominantly, but not exclusively, collagen type I fibers that are layered down in oriented linear bundles. This protein matrix scaffold is coated with a layer of mineral, predominantly calcium phosphate in the form of crystals of hydroxyapatite [1]. The skeleton forms in early life, mainly through endochondral ossification in which bone is initially patterned in mineralized cartilage followed by replacement of the cartilage template by mineralized bone. Some skeletal components including certain bones of the skull such as the calvaria are formed without a cartilage intermediate through direct matrix and mineralization deposition, a process referred to as intramembranous ossification [2]. The skeleton achieves its final shape and ultimate form through bone modeling, a process involving the coordinated activity of bone synthesizing osteoblasts and bone resorbing osteoclasts. This process of selective bone deposition and removal sculpts the skeleton to achieve final shape and optimal load bearing capacity [3, 4]. Bone modeling continues until early adulthood in humans at which time peak bone mineral density (BMD) and bone size are achieved. Thereafter, the skeleton undergoes a process
%U http://www.hindawi.com/journals/scientifica/2013/125705/