Mitochondrial Biogenesis as a Therapeutic Target for Rotator Cuff Tendon Tears.

Rotator Cuff Injuries (RCI) are highly prevalent and characterized by shoulder pain, restricted shoulder movement, and difficulty with overhead activity, radiating pain in the deltoid muscle, and atrophy of the rotator cuff muscles. Increasing age, hand dominance, smoking, hypertension, hyperlipidemia, and obesity are common risk factors. Chronic inflammation plays a critical role in the underlying pathogenesis. RCI accounts for massive healthcare expenditure costing about $15,000 per repair, and over 4.5 million physician visits per year, however, there is still no therapeutic target to improve clinical outcomes. Mitochondrial biogenesis in response to inflammatory stimuli supports increased cellular energy requirements, cell proliferation, and differentiation. This suggests that mitochondrial biogenesis may play a role in healing RCI by serving as a protective factor against free oxygen species and promoting homeostasis within the rotator cuff. There is evidence highlighting the potential therapeutic benefits of mitochondrial biogenesis in various inflammatory diseases, but no study explored the role of mitochondrial biogenesis in rotator cuff tears. Since hypercholesterolemia is a risk factor for RCI, we investigated the effects of hypercholesterolemia on the expression of PGC-1α, a marker of mitochondrial biogenesis, in rotator cuff muscle. The findings revealed an increased gene and protein expression of inflammatory mediators and PGC-1α, suggesting enhanced inflammation and increased mitochondrial biogenesis due to hypercholesterolemia. Additional studies are warranted to further investigate the chronic effect of hyperlipidemia induced RCI to elucidate the cause of insufficient mitochondrial biogenesis unable to protect the rotator cuff and the therapeutic effect of promoting mitochondrial biogenesis.