Cellular and Molecular Aspects of Bone Remodeling

Abstract

Bone remodeling is a highly coordinated process responsible for bone resorption and formation. It is initiated and modulated by a number of factors including inflammation, changes in hormonal levels and lack of mechanical stimulation. Bone remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix through osteoblasts that subsequently becomes mineralized. In addition to the traditional bone cells (osteoclasts, osteoblasts and osteocytes) that are necessary for bone remodeling, several immune cells such as polymorphonuclear neutrophils, B cells and T cells have also been implicated in bone remodelling. Through the receptor activator of nuclear factor-x03BA;B/receptor activator of the NF-x03BA;B ligand/osteoprotegerin system the process of bone resorption is initiated and subsequent formation is tightly coupled. Mediators such as prostaglandins, interleukins, chemokines, leukotrienes, growth factors, wnt signalling and bone morphogenetic proteins are involved in the regulation of bone remodeling. We discuss here cells and mediators involved in the cellular and molecular machanisms of bone resorption and bone formation.

Fig. 1.

Stimulation of osteoclastogenesis, bone resorption, and coupled bone formation. RANKL, M-CSF, and TNF directly stimulate the formation of osteoclasts, while other cytokines or lipid-based mediators such as prostaglandins or leukotrienes indirectly stimulate osteoclastogenesis by effects on RANKL, M-CSF, or TNF-α. Chemokines affect resorption by stimulation recruitment of osteoclast precursors or osteoclast activity. Chemokines such as CXCL10, CXCL12, CXCL13, and CCL5, may affect bone formation by effects on osteoblast precursors or osteoblasts. Wnt signaling, growth factors such as FGF, PDGF, BMP-2, TGF-β, and IGF play an important role in osteogenesis by stimulating proliferation of mesenchymal stem cells/osteoblast precursors and inducing osteoblast differentiation or synthesis of bone matrix. Modified with permission from Graves et al. [30].