期刊
IMMUNE NETWORK
卷 22, 期 3, 页码 -出版社
KOREA ASSOC IMMUNOLOGISTS
DOI: 10.4110/in.2022.22.e25
关键词
IL34; Osteonecrosis; Osteoclast; M-CSF; Inflammation
类别
资金
- National Natural Science Foundation of China [81873993]
- Clinical Science and Technology Innovation Project of Shanghai Hospital Development Center [SHDC12019X24]
- Shanghai Pudong New Area Science and Technology Development Fund [PKJ2019-Y02]
IL-34 promotes osteoclast differentiation and activation, aggravating steroid-induced osteonecrosis of the femoral head (ONFH). IL-34 expression is up-regulated in patients with ONFH and femoral heads of ONFH mice, while IL-34 deficient mice show resistance to ONFH induction. IL-34 works in coordination with M-CSF to promote osteoclastogenesis and activates ERK, STAT3, and non-canonical NF-kappa B pathways.
IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-alpha, IFN-gamma, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-kappa B pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-kappa B pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.
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