High resolution

Module 8: Figure osteoclastogenesis

Summary of osteoclastogenesis.

Osteoclastogenesis is the developmental process responsible for forming osteoclasts. A number of cells contribute by providing various ligands. The stromal cells provide colony-stimulating factor-1 (CSF-1). The osteoblasts and T cells present receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). They also release osteoprotegerin (OPG), which is a soluble RANKL-binding decoy receptor that inhibits the action of RANKL receptor (RANK). Parathyroid hormone (PTH) promotes bone resorption by inhibiting the release of OPG and enhancing the expression of RANKL. Another group of immunological-like receptors [osteoclast-associated receptor (OSCAR), paired immunoglobin-like receptor (PIR-A), triggering receptor expressed in myeloid cells (TREM-2) and signal-regulatory protein (SIRPβ1)] provide co-stimulatory signals. The CSF-1 receptor (CSF-1R) not only inhibits apoptosis, but also induces inside-out integrin signalling, which facilitates integrin binding to bone. The osteoblasts and osteoclasts communicate with each other through the ephrin (Eph) receptor signalling pathway. The way in which these receptors function to regulate apoptosis, proliferation and differentiation are described in Module 8: Figure osteoclast differentiation.