Hif-1 Alpha Repairs Degenerative Chondrocyte Glycolytic Metabolism By The Transcriptional Regulation Of Runx2

OBJECTIVE: HIF-1 alpha and Runx2 expression usually increase in chondrocytes (CHs) during osteoarthritis (OA), which involves the changes in glycolytic metabolism. However, the molecular regulation of HIF-1 alpha related to the CHs glycolytic metabolism is still unclear. In this study, we aimed to reveal the mediation of HIF-1 alpha by Runx2 and its effect on the glycolytic metabolism of degenerative CHs.PATIENTS AND METHODS: The expression of HIF-1 alpha, Runx2, and the degenerative markers of CHs in both natural conditions from the OA patients and IL-1 beta treated in vitro model was analyzed by a Western blot or real-time polymerase chain reaction (RT-PCR). The glycolytic metabolism was determined by the intracellular glucose uptake and adenosine triphosphate (ATP) generation. Transfection of siRNA coding HIF-1 alpha or Runx2 was used to clear the function between HIF-1 alpha and Runx2 in the glycolytic metabolism of degenerated CHs caused by IL-1 beta. Chromatin immunoprecipitation (ChIP) and Luciferase reporter gene assay were used to verify the Runx2 protein binds to the promoter of HIF-1 alpha and promote its expression.RESULTS: HIF-1 alpha and Runx2 were increased, and glucose uptake and ATP generation were decreased in the degenerative CHs from both OA and IL-1 beta conditions. Under the stimulation of IL-1 beta, Runx2 silencing rejected the upregulation of HIF-1 alpha and further aggravated the glycolytic metabolism. When HIF-1 alpha was silenced, the glycolytic metabolism of CHs was also suppressed. Besides, Runx2 protein could regulate HIF-1 alpha expression in the transcriptional level by binding to its promoter.CONCLUSIONS: OHIF-1 alpha plays a role in the self-repair of the glycolytic metabolism of degenerative CHs via the transcriptional regulation of Runx2.