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MEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS
Takayuki Fujii1, Koichi Murata1,2,3, Se-Hwan Mun1
1Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Bone Research
|January 11, 2021
Summary
MEF2C regulates osteoclast differentiation, a key process in bone resorption. This study reveals MEF2C
Area of Science:
- Bone Biology and Metabolism
- Cellular and Molecular Medicine
Background:
- Osteoporosis is characterized by reduced bone mineral density due to imbalanced bone remodeling.
- The MEF2C gene is linked to osteoporosis and fractures, but its role in osteoclasts is unknown.
- Osteoclasts are crucial for bone resorption, a process dysregulated in metabolic bone diseases.
Purpose of the Study:
- To investigate the role of MEF2C in osteoclast differentiation and function.
- To elucidate the molecular mechanisms by which MEF2C influences osteoclastogenesis.
- To evaluate the therapeutic potential of targeting MEF2C in bone loss conditions.
Main Methods:
- Assessed MEF2C's impact on osteoclast differentiation in vitro using human and mouse cells.
- Employed transcriptomic and bioinformatic analyses to identify MEF2C-regulated genes.
- Utilized inducible Mef2c deletion in mice to study its in vivo effects on bone mass and arthritis models.
Main Results:
- MEF2C acts as a positive regulator of osteoclast differentiation; reduced MEF2C impairs osteoclastogenesis, while increased MEF2C enhances it.
- MEF2C promotes RANKL-induced expression of c-FOS and NFATc1, critical transcription factors for osteoclast formation.
- MEF2C directly binds to FOS regulatory regions, driving c-FOS expression and subsequent NFATc1 activation.
- Mice with Mef2c deletion exhibited increased bone mass and protection against inflammatory arthritis-induced bone erosion.
Conclusions:
- MEF2C directly regulates osteoclast differentiation and function.
- Targeting MEF2C offers a potential strategy for treating osteoporosis and related bone disorders.
- This study identifies osteoclasts as a key cell type influenced by MEF2C in pathological bone remodeling.
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