Research on E3 ubiquitin ligase TRIM22 knockdown regulating macrophage polarization and osteoclast differentiation...

The balance of the activities of osteoclasts (OCs) and osteoblasts is essential for maintenance of bone homeostasis. Macrophages polarizing into a pro-inflammatory M1 type are responsible for differentiation of OCs. This project aims to explore the role of tripartite motif containing 22 (TRIM22), a member of the TRIM proteins with pivotal roles in bone immune response, in macrophage polarization and OC differentiation.

Bone marrow macrophages (BMMs) were isolated from femurs and tibias of C57BL/6 mice and stimulated with macrophage colony-stimulating factor (M-CSF) and RANKL to form OCs. LPS and IL-4 were used to induce polarization of BMMs into M1 and M2 macrophages, respectively. RT-qPCR and Western blot assays were conducted to examine the expression of TRIM22 during OC differentiation. The functions of TRIM22 on M1 macrophage polarization and OC differentiation were assessed utilizing loss-of-function experiments in vitro.

Increased expression of TRIM22 was found during OC differentiation, while its knockdown in BMMs alleviated OC formation. M1 polarization of BMMs facilitated OC differentiation as opposed to the M2 phenotype that exhibited anti-OC differentiation characteristics. TRIM22 deficiency attenuated M1 macrophage polarization and inflammatory cytokine secretion, concomitant with suppressed OC differentiation. The NF-κB/MAPK pathway inactivation was responsible for this effect of TRIM22 knockdown.

These results reveal a critical mechanism for OC differentiation which is mediated by the TRIM22/NF-κB/MAPK signaling, highlighting a possible avenue for further exploration of target molecules in bone diseases.