Osteoclast–osteoblast communication

Cells in osteoclast and osteoblast lineages communicate with each other through cell–cell contact, diffusible paracrine factors and cell–bone matrix interaction. Osteoclast–osteoblast communication occurs in a basic multicellular unit (BMU) at the initiation, transition and termination phases of bone remodeling. At the initiation phase, hematopoietic precursors are recruited to the BMU. These precursors express cell surface receptors including c-Fms, RANK and costimulatory molecules, such as osteoclast-associated receptor (OSCAR), and differentiate into osteoclasts following cell–cell contact with osteoblasts, which express ligands. Subsequently, the transition from bone resorption to formation is mediated by osteoclast-derived ‘coupling factors’, which direct the differentiation and activation of osteoblasts in resorbed lacunae to refill it with new bone. Bidirectional signaling generated by interaction between ephrinB2 on osteoclasts and EphB4 on osteoblast precursors facilitates the transition. Such interaction is likely to occur between osteoclasts and lining cells in the bone remodeling compartment (BRC). At the termination phase, bone remodeling is completed by osteoblastic bone formation and mineralization of bone matrix. Here, we describe molecular communication between osteoclasts and osteoblasts at distinct phases of bone remodeling.