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

Minhee Kim, Jingjing Lin, Jeong Eun Huh, Jin Hee Park, Miyeon Go, Hana Lee, Donghyun Hwang, Han Sung Kim, Taesoo Kim, Daekee Lee, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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-кB/αvβ3 integrin. Overall, our findings suggest that TSPAN7 acts as a novel modulator regulating the bone-resorbing function of osteoclasts.

Original languageEnglish
Pages (from-to)846-855
Number of pages10
JournalJournal of Cellular Physiology
Volume237
Issue number1
DOIs
StatePublished - Jan 2022

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