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Tetraspanin 7 regulates osteoclast function through association with the RANK/αvβ3 integrin complex
Minhee Kim1,2, Jingjing Lin1,2, Jeong-Eun Huh1,2
1Department of Life Science, Ewha Womans University, Seoul, South Korea.
Journal of Cellular Physiology
|August 18, 2021
Summary
Tetraspanin7 (TSPAN7) is crucial for osteoclast function in bone resorption. Deleting the gene for TSPAN7 impairs actin ring formation and reduces bone loss, suggesting TSPAN7 regulates osteoclast activity.
Area of Science:
- Cell Biology
- Skeletal Biology
- Molecular Biology
Background:
- Actin rings are vital for osteoclast attachment and bone resorption.
- Tetraspanin7 (TSPAN7) is implicated in cytoskeletal reorganization for osteoclast activity.
- The precise mechanisms of TSPAN7's role in cytoskeletal regulation remain unclear.
Purpose of the Study:
- To investigate the function of TSPAN7 in osteoclasts.
- To elucidate the role of TSPAN7 in regulating cytoskeletal rearrangement and bone resorption.
- To determine the association of TSPAN7 with key signaling molecules in osteoclasts.
Main Methods:
- Generated Tm4sf2 global knockout mice (encoding TSPAN7).
- Assessed bone phenotypes in vivo under physiological and pathological conditions.
- Conducted in vitro studies to evaluate actin ring formation and bone resorption in TSPAN7-ablated osteoclasts.
- Investigated the association between TSPAN7 and the receptor activator of nuclear factor-κB/αvβ3 integrin.
Main Results:
- Tm4sf2 knockout mice exhibited protection against pathological bone loss.
- No significant bone phenotype changes were observed under physiological conditions.
- Ablation of Tm4sf2 led to defects in integrin-mediated actin ring formation in vitro.
- TSPAN7 deficiency resulted in significantly decreased bone resorption.
- An association between TSPAN7 and the receptor activator of nuclear factor-κB/αvβ3 integrin was identified.
Conclusions:
- TSPAN7 plays a significant role in regulating osteoclast actin ring formation and bone resorption.
- TSPAN7 deficiency protects against pathological bone loss by impairing osteoclast function.
- TSPAN7 is a novel modulator of osteoclast bone-resorbing activity, potentially via interaction with the RANK/αvβ3 integrin pathway.
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