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Updated: Jun 20, 2025
Development of a Rabbit Chronic-Like Rotator Cuff Injury Model for Study of Fibrosis and Muscular Fatty Degeneration
Published on: March 31, 2023
Overexpression of PRDM16 improves muscle function after rotator cuff tears
He Zhang1, Aboubacar Wague2, Agustin Diaz2
1Department of Physical Education, Central South University, Changsha, Hunan, China; Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Orthopedic Surgery, University of California, San Francisco, San Francisco, CA, USA.
Elevated PRDM16 levels improved rotator cuff tear (RCT) outcomes by enhancing muscle function and reducing fatty infiltration. This suggests promoting brown adipose tissue (BAT) activity can aid shoulder function recovery after RCT.
Area of Science:
- Biomedical research
- Muscle and adipose tissue biology
- Regenerative medicine
Background:
- Rotator cuff tears (RCTs) often lead to muscle atrophy, fibrosis, and fatty infiltration, negatively impacting patient outcomes.
- Improving muscle quality post-RCT is critical for successful tendon repair and functional recovery.
- Functional beige/brown adipose tissue (BAT) secretes batokines that can promote muscle growth, with PRDM16 being a key regulator of brown fat development.
Purpose of the Study:
- To investigate the role of PRDM16 in enhancing muscle function following massive tendon tears.
- To utilize a transgenic mouse model with elevated PRDM16 expression to study its effects on rotator cuff muscle quality.
Main Methods:
- Transgenic PRDM16-overexpressing mice and wild-type controls underwent rotator cuff and suprascapular nerve transection (TTDN).
- Forelimb function was assessed using DigiGait at 6 weeks post-injury.
- Muscle fibrosis, fatty infiltration, and fiber type (MHC expression) were analyzed via Masson Trichrome, Oil Red O, and immunostaining, respectively.
Main Results:
- PRDM16 overexpression increased PRDM16 protein in both white and brown fat tissues.
- Despite no change in muscle weight, PRDM16 overexpression significantly improved forelimb function (longer stance, stride time, larger stride length/paw area).
- Fatty infiltration was significantly reduced, while fibrosis remained unchanged; increased MHC-IIx fiber percentage was observed in supraspinatus muscle.
Conclusions:
- PRDM16 overexpression significantly enhances muscle function and reduces fatty infiltration after rotator cuff tears.
- Activating brown adipose tissue (BAT) shows promise for improving rotator cuff muscle quality and shoulder function post-RCT.
