Abstract
BackgroundThe rotator cuff undergoes natural degeneration with age, leading to age-related rotator cuff tear; however, the precise mechanism remains unclear. Transforming growth factor-beta (TGF-β) concentrations rise with age and TGF-β contributes to the pathophysiology of skeletal muscle. TGF-β has also been shown to suppress expression of the myokine, apelin, in skin fibroblasts. We hypothesized that TGF-β expression in the rotator cuff changes with age and regulates apelin expression, thereby contributing to rotator cuff degeneration.MethodsWe used quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) to measure the expression of apelin and tendon-related genes (Tnmd, Col1a1, and Col3a1) in the rotator cuff of young (12 weeks), adult (24 weeks), and old (48 weeks) rats. Using Q-RT-PCR and enzyme-linked immunosorbent assay, we also measured Tgfb mRNA and TGF-β protein levels, respectively. Furthermore, we used Q-RT-PCR to measure apelin mRNA levels in rotator cuff-derived cells after treatment with 0 (control) and 10 ng/mL recombinant TGF-β.ResultsApelin mRNA levels were significantly lower in old compared to young and adult rats. Similarly, tendon-related genes, Tnmd, Col1a1, and Col3a1, were significantly lower in adult and old rats than young rats. In contrast, Tgfb mRNA and TGF-β protein were significantly higher in old compared to young rats. Stimulation with exogenous TGF-β significantly decreased Apelin mRNA expression compared to control.ConclusionsTGF-β regulates apelin expression in the rotator cuff and may play a key role in the degenerative pathology of the rotator cuff with age.
Highlights
The rotator cuff undergoes natural degeneration with age, leading to age-related rotator cuff tear; the precise mechanism remains unclear
The supraspinatus is responsible for initiating abduction of the glenohumeral joint (GHJ) [2], the infraspinatus and teres minor for external rotation, and the subscapularis for internal rotation of the GHJ [2
We examined age-related changes in TGF-β and apelin expression and the relationship between TGF-β and apelin in the rat rotator cuff
Summary
The rotator cuff undergoes natural degeneration with age, leading to age-related rotator cuff tear; the precise mechanism remains unclear. We hypothesized that TGF-β expression in the rotator cuff changes with age and regulates apelin expression, thereby contributing to rotator cuff degeneration. The rotator cuff consists of four muscle/tendon units, the supraspinatus, infraspinatus, subscapularis, and teres minor, originate at the scapula and insert into the proximal humerus [1]. Evidence suggests [7, 8] that a combination of extrinsic factors such as greater subacromial loading [9] and muscle imbalance, and intrinsic factors such as age-related degeneration [10, 11] contribute to the development of RCT. The incidence of RCT rises with age, with approximately 30% of cases aged ≥ 60 years [13]
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