Regenerative Therapy (Dec 2022)
Hypoxia inducible factor-1α mediates the mechanism of the Hedgehog pathway in tendinopathy repair by Asperosaponin VI
Abstract
Background: Our previous study found that asperosaponin VI (ASA VI) has a positive effect on the repair of tendinopathy. However, its molecular biological mechanism is unclear. Objective: To investigate the role of hypoxia inducible factor-1α (HIF-1α) in mediating the hedgehog (Hh) pathway in tendinopathy repair by ASA VI. Methods: A total of 36 2-month-old female SD rats were classified into the normal group (NG, n = 10) and tendinopathy model group (n = 26). The tendinopathy model group was further divided into the model group (MG), ASA VI group (AG), and triamcinolone acetonide + lidocaine group (TG). Results: Compared with those in the MG group, IL-1 mRNA was significantly downregulated and IL-4 and IL-10 were increased in the AG group (P < 0.01). The mRNA expression levels of MMP3, TIMP3, VEGF-A, KDR, and VWF mRNA decreased (P < 0.01). Immunofluorescence staining revealed that CD31/endomucin levels were significantly attenuated. Scx, Mkx, EYA1, EYA2, COL1, COL3, and TNC mRNA levels showed significant differences (P < 0.01). Immunofluorescence staining suggested the upregulation of Scx and the downregulation of Sox9. Shh, Ptch1, Smo, Gli1, Cyc-D1, Cyc-E1, and c-Myc mRNA levels were downregulated (P < 0.01). The protein expression levels of Gli 1, Shh, and Ptch1 decreased significantly (P < 0.01). The immunofluorescence staining levels of Shh, Ptch, and Gli 1 significantly decreased. Conclusion: ASA VI inhibits local vascular hyperproliferation and downregulates the HIF-1α/Hh pathway to promote the tendinous differentiation of tendon stem/progenitor cells and the repair of tendinopathy. The effect of ASA VI on HIF-1α levels may be an effective target in the treatment of tendinopathy.
