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Updated: Nov 16, 2025
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Published on: November 13, 2013
Ccn6 Is Required for Mitochondrial Integrity and Skeletal Muscle Function in Zebrafish
Archya Sengupta1, Deepesh Kumar Padhan1, Ananya Ganguly1
1Division of Cancer Biology & Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Abstract:
Mutations in the CCN6 (WISP3) gene are linked with a debilitating musculoskeletal disorder, termed progressive pseudorheumatoid dysplasia (PPRD). Yet, the functional significance of CCN6 in the musculoskeletal system remains unclear. Using zebrafish as a model organism, we demonstrated that zebrafish Ccn6 is present partly as a component of mitochondrial respiratory complexes in the skeletal muscle of zebrafish. Morpholino-mediated depletion of Ccn6 in the skeletal muscle leads to a significant reduction in mitochondrial respiratory complex assembly and activity, which correlates with loss of muscle mitochondrial abundance. These mitochondrial deficiencies are associated with notable architectural and functional anomalies in the zebrafish muscle. Taken together, our results indicate that Ccn6-mediated regulation of mitochondrial respiratory complex assembly/activity and mitochondrial integrity is important for the maintenance of skeletal muscle structure and function in zebrafish. Furthermore, this study suggests that defects related to mitochondrial respiratory complex assembly/activity and integrity could be an underlying cause of muscle weakness and a failed musculoskeletal system in PPRD.
Insights
CCN6 (WISP3) protein is crucial for mitochondrial function in skeletal muscles. Its depletion impairs mitochondrial complexes, leading to muscle defects, suggesting a role in progressive pseudorheumatoid dysplasia.
Area of Science:
- Molecular Biology
- Genetics
- Zebrafish Models
Background:
- Mutations in the CCN6 (WISP3) gene cause progressive pseudorheumatoid dysplasia (PPRD), a severe musculoskeletal disorder.
- The precise role of CCN6 in musculoskeletal health is not fully understood.
Purpose of the Study:
- To investigate the functional significance of CCN6 in skeletal muscle maintenance.
- To explore the molecular mechanisms underlying CCN6's role in muscle function using a zebrafish model.
Main Methods:
- Utilized zebrafish as a model organism to study Ccn6 function.
- Employed morpholino-mediated depletion to reduce Ccn6 levels in skeletal muscle.
- Analyzed mitochondrial respiratory complex assembly, activity, and abundance.
- Assessed skeletal muscle architecture and function.
Main Results:
- Zebrafish Ccn6 was identified as a component of mitochondrial respiratory complexes in skeletal muscle.
- Ccn6 depletion resulted in reduced mitochondrial respiratory complex assembly and activity.
- Loss of Ccn6 led to decreased mitochondrial abundance and muscle structural/functional deficits.
- Mitochondrial deficiencies correlated with impaired skeletal muscle integrity.
Conclusions:
- CCN6 plays a vital role in regulating mitochondrial respiratory complex assembly, activity, and integrity in skeletal muscle.
- These findings highlight the importance of CCN6 for maintaining skeletal muscle structure and function.
- Defects in CCN6-dependent mitochondrial function may underlie the muscle weakness observed in progressive pseudorheumatoid dysplasia (PPRD).
