HIF-1α inhibition attenuates severity of Achilles tendinopathy by blocking NF-κB and MAPK pathways.

Tendinopathy is a common disease influencing life quality and tendon function of patients, especially in the elderly and athletes. Inflammation is an important pathologic process of tendinopathy. Hypoxia inducible factor-1 alpha (HIF-1α) participates actively in inflammatory process. However, little is known about the role of HIF-1α in tendinopathy. To address this issue, we verified the expression level of HIF-1α in tendinopathy in vivo and in vitro. Furthermore, the severity of tendinopathy in vivo and in vitro was assessed after HIF-1α inhibition. At the same time, inflammatory signaling cascades were evaluated. The expression level of HIF-1α increased in tendinopathy in vivo and in vitro. The migration and proliferation of tendon cells (TDCs) were reduced after HIF-1α inhibition. In the meantime, HIF-1α inhibition alleviated the severity of tendinopathy and promoted tendon repairing. We also found that HIF-1α inhibition reduced the phosphorylation levels of p65 in NF-κB signaling pathway and the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and Jun N-terminal kinase (JNK) in MAPK signaling pathway. These findings suggest that HIF-1α increases in tendinopathy in vivo and vitro, and HIF-1α inhibition can suppress the severity of tendinopathy by blocking NF-κB and MAPK signaling pathways.