Tetraspanin 7 regulates osteoclast function through association with the RANK/αvβ3 integrin complex

Actin rings are unique structures that facilitate the attachment of osteoclasts to the bone matrix during bone resorption. Previous studies have shown that tetraspanin7 (TSPAN7) plays an important role in the reorganization of the cytoskeleton necessary for the bone-resorbing activity of osteoclasts. However, questions remain as to the mechanisms by which TSPAN7 regulates this cytoskeletal rearrangement. In this study, we investigated the roles of TSPAN7 in osteoclasts by deleting the Tm4sf2 gene in mice, which encodes TSPAN7. The Tm4sf2 global knockout model showed protective effects on pathological bone loss, but no discernible changes in bone phenotypes under physiological conditions. In vitro study revealed that ablation of Tm4sf2 caused significant defects in integrin-mediated actin ring formation, thereby leading to significantly decreased bone resorption. Additionally, we demonstrated an association between TSPAN7 and the receptor activator of nuclear factor-kB/alpha v beta 3 integrin. Overall, our findings suggest that TSPAN7 acts as a novel modulator regulating the bone-resorbing function of osteoclasts.

Automated summary

The study revealed that TSPAN7 plays a crucial role in regulating the bone-resorbing function of osteoclasts by modulating actin ring formation. Deletion of Tm4sf2 led to significant defects in integrin-mediated actin ring formation, resulting in decreased bone resorption. The findings suggest that TSPAN7 acts as a novel modulator in osteoclasts.