IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappaB (RANK) expression in myeloid precursor cells.
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-kappaB expression in primary murine bone marrow macrophages and RAW264.7 cells and thereby promotes commitment of myeloid precursor cells to receptor activator of NF-kappaB 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-kappaB ligand production in osteoblasts and explains its potency in driving osteoclast development in inflammation-mediated bone pathology.
Chen
Li
L
Orthodontic Department, School of Stomatology, Capital Medical University, Beijing, China, and Matrix Biology and Tissue Repair Research Unit, School of Dentistry, Cardiff University, UK.
Wei
Xiao-Qing
XQ
Evans
Bronwen
B
Jiang
Wenguo
W
Aeschlimann
Daniel
D
D000818:Animals; D002454:Cell Differentiation; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D023461:Myeloid Progenitor Cells / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015854:Up-Regulation
C486767:Il27 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins; C505687:Tnfrsf11a protein, mouse