| First Author | Miao J | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1425670 | PubMed ID | 39281679 |
| Mgi Jnum | J:359146 | Mgi Id | MGI:7731542 |
| Doi | 10.3389/fimmu.2024.1425670 | Citation | Miao J, et al. (2024) hFcgammaRIIa: a double-edged sword in osteoclastogenesis and bone balance in transgenic mice. Front Immunol 15:1425670 |
| abstractText | Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcgammaRs, especially FcgammaRIIa (hFcgammaRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcgammaRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcgammaRIIa on osteoclast differentiation through investigations involving hFcgammaRIIa-transgenic (hFcgammaRIIa-Tg) mice. Our findings reveal that hFcgammaRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcgammaRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-kappaB ligand (RANKL). Additionally, hFcgammaRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcgammaRIIa. Mechanistically, bone marrow cells from hFcgammaRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcgammaRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcgammaRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders. |
