Abstract
Formation of mature bone-resorbing cells through osteoclastogenesis is required for the continuous remodeling and repair of bone tissue. In aging and disease this process may become aberrant, resulting in excessive bone degradation and fragility fractures. Interaction of receptor-activator of nuclear factor-κB (RANK) with its ligand RANKL activates the main signaling pathway for osteoclastogenesis. However, compelling evidence indicates that this pathway may not be sufficient for the production of mature osteoclast cells and that co-stimulatory signals may be required for both the expression of osteoclast-specific genes and the activation of osteoclasts. Osteoclast-associated receptor (OSCAR), a regulator of osteoclast differentiation, provides one such co-stimulatory pathway. This review summarizes our present knowledge of osteoclastogenesis signaling and the role of OSCAR in the normal production of bone-resorbing cells and in bone disease. Understanding the signaling mechanism through this receptor and how it contributes to the production of mature osteoclasts may offer a more specific and targeted approach for pharmacological intervention against pathological bone resorption.
Highlights
Reviewed by: Jiake Xu, University of Western Australia, Australia An Qin, Shanghai Ninth People’s Hospital, China Kai Chen, University of Western Australia, Australia
The requirement for co-stimulatory signaling through DNAXassociated protein of 12 kDa (DAP12) and FcεRI γ chain (FcRγ) for OCL differentiation was demonstrated by Koga et al (2004), who found that nuclear factor of activated T cells 1 (NFATc1) expression was nearly undetectable in DAP12−/− FcRγ−/− cells following stimulation with RANK ligand (RANKL), even though c-Fos and TNFR-associated factor 6 (TRAF6) were expressed
The authors proposed that OBL cells were likely expressing a putative Osteoclast-associated receptor (OSCAR) ligand. These findings are in agreement with studies that demonstrate that the rescue effects of FcRγ in osteoclastogenesis of DAP12−/− cells are observable only when the OCL precursors are co-cultured with OBLs (Koga et al, 2004; Mócsai et al, 2004)
Summary
Reviewed by: Jiake Xu, University of Western Australia, Australia An Qin, Shanghai Ninth People’s Hospital, China Kai Chen, University of Western Australia, Australia. The requirement for co-stimulatory signaling through DAP12 and FcRγ for OCL differentiation was demonstrated by Koga et al (2004), who found that NFATc1 expression was nearly undetectable in DAP12−/− FcRγ−/− cells following stimulation with RANKL, even though c-Fos and TRAF6 were expressed.
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