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Osteocytic vinculin controls bone mass by modulating Mef2c-driven sclerostin expression in mice
Yishu Wang1, Jianmei Huang1,2, Sixiong Lin1,3,4
1Department of Biochemistry, Homeostatic Medicine Institute School of Medicine Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen, China.
Bone Research
|August 12, 2025
Summary
Vinculin, a focal adhesion protein, is crucial for osteocyte function and bone formation. Loss of vinculin in osteocytes leads to reduced bone density by increasing sclerostin, a key regulator of bone metabolism.
Area of Science:
- Cell Biology
- Bone Biology
- Biochemistry
Background:
- Focal adhesions (FAs) mediate cell-extracellular matrix interactions vital for organ development.
- Osteoporosis, particularly age-related, is characterized by reduced bone mass and increased fracture risk.
- Osteocytes, embedded bone cells, play critical roles in bone maintenance and mechanotransduction.
Purpose of the Study:
- To investigate the role of the focal adhesion protein vinculin in osteocytes.
- To elucidate the molecular mechanisms by which vinculin influences bone formation and resorption.
- To determine the relationship between vinculin, sclerostin, and Mef2c in osteocyte function.
Main Methods:
- Utilized Dmp1-Cre transgenic mice for targeted deletion of vinculin in osteocytes.
- Assessed bone phenotypes, including bone mineral density and microarchitecture.
- Investigated osteoblast and osteoclast activity, and mechanical loading responses.
- Examined sclerostin and Mef2c expression and their interaction using molecular biology techniques.
- Studied the effect of estrogen and ovariectomy on vinculin expression.
Main Results:
- Vinculin expression is significantly reduced in osteocytes of patients with aging-related osteoporosis.
- Vinculin deficiency in osteocytes impairs cell adhesion, dendrite formation, and bone formation, leading to bone loss in long bones and spine.
- Vinculin loss enhances Mef2c nuclear translocation, promoting sclerostin expression and inhibiting bone formation.
- Deleting Sost in osteocytes rescues the osteopenic phenotype caused by vinculin loss.
- Estrogen regulates vinculin expression, and vinculin-deficient mice are resistant to ovariectomy-induced bone loss.
Conclusions:
- Vinculin is essential for osteocyte function and plays a protective role against osteoporosis.
- Vinculin acts as a negative regulator of Mef2c-driven sclerostin expression in osteocytes, thereby promoting bone formation.
- Targeting vinculin or its downstream pathways may offer therapeutic strategies for osteoporosis.
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