Skeletal muscle fibrosis and stiffness increase after rotator cuff tendon injury and neuromuscular compromise in a rat model.
Rotator cuff tears can cause irreversible changes (e.g., fibrosis) to the structure and function of the injured muscle(s). Fibrosis leads to increased muscle stiffness resulting in increased tension at the rotator cuff repair site. This tension influences repairability and healing potential in the clinical setting. However, the micro- and meso-scale structural and molecular sources of these whole-muscle mechanical changes are poorly understood. Here, single muscle fiber and fiber bundle passive mechanical testing was performed on rat supraspinatus and infraspinatus muscles with experimentally induced massive rotator cuff tears (Tenotomy) as well as massive tears with chemical denervation (Tenotomy + BTX) at 8 and 16 weeks post-injury. Titin molecular weight, collagen content, and myosin heavy chain profiles were measured and correlated with mechanical variables. Single fiber stiffness was not different between controls and experimental groups. However, fiber bundle stiffness was significantly increased at 8 weeks in the Tenotomy + BTX group compared to Tenotomy or control groups. Many of the changes were resolved by 16 weeks. Only fiber bundle passive mechanics was weakly correlated with collagen content. These data suggest that tendon injury with concomitant neuromuscular compromise results in extra-cellular matrix production and increases in stiffness of the muscle, potentially complicating subsequent attempts for surgical repair.
Department of Bioengineering, University of California San Diego, La Jolla, California, 92093.
Eugene J
EJ
Sato
Megan L
ML
Killian
Anthony J
AJ
Choi
Evie
E
Lin
Mary C
MC
Esparza
Leesa M
LM
Galatz
Stavros
S
Thomopoulos
Samuel R
SR
Ward
D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D064211:Connectin / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009129:Muscle Tonus / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009468:Neuromuscular Diseases / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000150:complications / Q000503:physiopathology*; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology
D064211:Connectin; D003094:Collagen
injury; muscle fibrosis; muscle passive mechanics; rotator cuff; shoulder