Role of Hypoxia-Inducible Factor-1α in Regulating Muscle Degeneration After Rotator Cuff Tears.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Secondary muscle degeneration after a rotator cuff tear (RCT) critically affects clinical outcomes. Vascular compromise after a tendon injury creates a complex microenvironment that may be associated with the degeneration of rotator cuff muscle. The role of hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular stress responses to hypoxia, in modulating muscle abnormalities after an RCT remains undefined. To define the role of HIF-1α in stem cell differentiation and muscle degeneration after an RCT in a murine model. Controlled laboratory study. A supraspinatus tendon transection and suprascapular nerve transection (TTDN) model was established in C57BL/6J, platelet-derived growth factor receptor α (PDGFRα)-green fluorescent protein (GFP) reporter, and inducible cell-specific HIF-1α knockout mice. Vascularity and HIF-1α colocalization with fibroadipogenic progenitor (FAP) cells and satellite cells were analyzed. Fibrosis, fatty infiltration, and myofiber cross-sectional area were assessed. In vitro, HIF-1α was modulated in isolated FAP cells via CRISPR-Cas9 or prolyl hydroxylase domain inhibitors to evaluate FAP cell differentiation. TTDN induced significant capillary density reduction (CD31 + ) at 1, 2, and 6 weeks after an injury. Global HIF-1α expression decreased after TTDN compared to the sham side (1 week: 0.78 ± 0.22 vs 1.40 ± 0.42, respectively [ P = .019];

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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