Up-regulated HIF-2α (hypoxia induced factor 2) had been demonstrated to contribute to Osteoarthritis (OA) development via inducing the expression of matrix-degrading enzymes. However, the HIF-2α also could promote primary cilia loss through HIF-2α/AURKA (Aurora kinase A)/NEDD9 pathway. And the primary cilia dysfunction is another characteristic of the OA. Thus, we investigated here whether the HIF-2α also contributes the OA development through mediating the primary cilia loss.
The primary chondrocytes were isolated from the experimental OA mice induced by destabilization of the medial meniscus (DMM). Chondrocytes were cultured under normoxia (21% O
Hypoxia could induce the expression of both HIF-1α and HIF-2α, and also reduce the number of primary cilia on the chondrocytes isolated from the experimental OA mice. Knocking-down or over-expressing HIF-1α or HIF-2α individually showed that the HIF-2α could induce the primary cilia reduction rather than the HIF-1α. Manipulating the HIF-2α expression could positively affect the AURKA and NEDD9 expression. Manipulating the AURKA and NEDD9 expressions could reverse the function of HIF-2α on primary cilia. In the mice, knocking-down both AURKA and NEDD9 could alleviate the OA development significantly.
Up-regulated HIF-2α contributes to the Osteoarthritis development through mediating the primary cilia loss, which might be developed as therapeutic targets for OA treatment.