Tripartite motif-containing 27 negatively regulates NF-κB activation in bone remodeling

Tripartite motif-containing 27 (TRIM27) is highly expressed in the mouse thymus, spleen, and hematopoietic compartment cells and regulates cell proliferation, apoptosis, and innate immune responses. However, the role of TRIM27 in bone remodeling remains unknown. This study aimed to investigate the role of TRIM27 in the differentiation of osteoclasts and osteoblasts.

We measured the effects of overexpression or knockdown of TRIM27 in osteoclasts and osteoblasts using real-time PCR and Western blot analysis to quantify the mRNA and protein levels of marker genes. Additionally, we performed an in vivo analysis of TRIM27 knockout mice through bone mineral density analysis and histological analysis.

TRIM27 deficiency decreased bone mineral density by enhancing osteoclast differentiation and inhibiting osteoblast differentiation. Overexpression of TRIM27 in osteoclast precursors suppressed osteoclast formation and resorption activity, and ectopic expression of TRIM27 in osteoblast precursors induced osteoblast differentiation and mineralization. Additionally, we found that TRIM27 attenuated NF-κB activation in both osteoclasts and osteoblasts by interacting with TAB2 and promoting TAB2 degradation through lysosomal-dependent pathways, thereby inhibiting NF-κB signaling.

Our results identify TRIM27 as a novel negative regulator of NF-κB in bone remodeling, suggesting that regulating TRIM27 may be useful in developing treatments for musculoskeletal diseases, such as osteoporosis.