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Updated: May 26, 2026
08:42
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Mef2c deletion in osteocytes results in increased bone mass
Ina Kramer1, Stefan Baertschi, Christine Halleux
1Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma, Basel, Switzerland.
Summary
Myocyte enhancer factor 2c (Mef2c) regulates bone mass by controlling osteoclast activity, not solely through Sost expression. Mef2c deficiency increases bone density by reducing bone resorption.
Area of Science:
- Bone Biology
- Genetics
- Endocrinology
Background:
- Myocyte enhancer factors 2 (MEF2) are implicated in bone biology, potentially regulating Sost expression.
- The in vivo role of Mef2c in osteocytes during skeletal development and aging remains to be fully elucidated.
Purpose of the Study:
- To investigate the in vivo function of Mef2c in osteocytes.
- To determine Mef2c's role in regulating bone mass, Sost expression, and bone remodeling during skeletal growth and aging.
Main Methods:
- Conditional knockout mice with Mef2c deficiency specifically in osteocytes (Dmp1-Cre) were generated.
- Bone mass, density, and cellular parameters of bone formation and resorption were analyzed.
- Expression of Sost, OPG, Sfrp2, and Sfrp3 was quantified in Mef2c mutant mice and compared to controls and Sost heterozygotes.
Main Results:
- Mef2c deficiency in osteocytes led to decreased Sost expression and increased bone mass, cortical thickness, and trabecular density.
- Increased bone mass in Mef2c mutants was not directly linked to reduced Sost expression, as Sost heterozygotes showed different effects.
- Mef2c deficiency significantly decreased bone resorption and increased osteoprotegerin (OPG) expression, suggesting a role in regulating osteoclast activity.
Conclusions:
- Mef2c plays a crucial role in regulating adult bone mass by controlling osteoclastic bone resorption.
- Mef2c regulates Sost expression in vivo and influences Wnt signaling modulators Sfrp2 and Sfrp3.
- The increased bone mass observed in Mef2c mutants is primarily due to reduced bone resorption, independent of Sost levels.
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