Fig. 2

Schematic representation of bone remodelling and underlying pathogenetic mechanisms. During bone remodelling, osteoclasts are derived from hematopoietic cells, while osteoblasts are derived from bone marrow mesenchymal stem cells (BMSCs). The Wnt/β-catenin signalling pathway activates its ligands, thus promoting bone formation. The regulation of osteoclastogenesis involves the interaction between osteoblasts and osteoclast precursors. Osteoclast differentiation is promoted when the receptor activator of RANK (expressed by osteoclast precursors) binds to its ligand RANKL. However, osteoprotegerin (OPG), which is secreted by osteoblasts, competes with RANK for binding to RANKL, thereby reducing signalling to osteoclasts. This negative feedback loop suppresses osteoclast differentiation, thus making the OPG/RANK/RANKL system crucial for regulating osteoclast activity and differentiation