Abstract
Inflammation‐mediated bone loss is a major feature of various bone diseases including rheumatoid arthritis, osteoarthritis and advanced periodontitis. Enhanced osteoclast development or activity at the inflammation site results in bone resorption. IL‐23 is a heterodimeric cytokine belonging to the IL‐6/IL‐12 family that has been implicated in the pathogenesis of rheumatoid arthritis and demonstrated to play a role in osteoclastogenesis via stimulation of IL‐17 production. In this study we investigated whether IL‐23 contributes to the regulation of osteoclast differentiation independent of the IL‐17 pathway. We show that IL‐23 dose‐dependently up‐regulates receptor activator of NF‐κB expression in primary murine bone marrow macrophages and RAW264.7 cells and thereby promotes commitment of myeloid precursor cells to receptor activator of NF‐κB ligand‐mediated osteoclastic differentiation. However, IL‐23 by itself is insufficient to induce osteoclastogenesis. Increased osteoclastic differentiation of cells was associated with enhanced cathepsin K expression and dentine resorption indicating enhanced formation of functional osteoclasts. IL‐17 was not detectable in culture supernatants and when added to cultures, did not promote differentiation of RAW264.7 cells. These results demonstrate that IL‐23 can act directly on myeloid precursor cells in addition to indirectly stimulating receptor activator of NF‐κB ligand production in osteoblasts and explains its potency in driving osteoclast development in inflammation‐mediated bone pathology.