HIF-1α repairs degenerative chondrocyte glycolytic metabolism by the transcriptional regulation of Runx2

P. Kong, R. Chen, F.-Q. Zou, Y. Wang, M.-C. Liu, W.-G. Wang

The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. 2015020670@stu.sdnu.edu.cn

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• Orthopedics

OBJECTIVE: HIF-1α and Runx2 expression usually increase in chondrocytes (CHs) during osteoarthritis (OA), which involves the changes in glycolytic metabolism. However, the molecular regulation of HIF-1α related to the CHs glycolytic metabolism is still unclear. In this study, we aimed to reveal the mediation of HIF-1α by Runx2 and its effect on the glycolytic metabolism of degenerative CHs.

PATIENTS AND METHODS: The expression of HIF-1α, Runx2, and the degenerative markers of CHs in both natural conditions from the OA patients and IL-1β 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-1α or Runx2 was used to clear the function between HIF-1α and Runx2 in the glycolytic metabolism of degenerated CHs caused by IL-1β. Chromatin immunoprecipitation (ChIP) and Luciferase reporter gene assay were used to verify the Runx2 protein binds to the promoter of HIF-1α and promote its expression.

RESULTS: HIF-1α and Runx2 were increased, and glucose uptake and ATP generation were decreased in the degenerative CHs from both OA and IL-1β conditions. Under the stimulation of IL-1β, Runx2 silencing rejected the upregulation of HIF-1α and further aggravated the glycolytic metabolism. When HIF-1α was silenced, the glycolytic metabolism of CHs was also suppressed. Besides, Runx2 protein could regulate HIF-1α expression in the transcriptional level by binding to its promoter.

CONCLUSIONS: OHIF-1α plays a role in the self-repair of the glycolytic metabolism of degenerative CHs via the transcriptional regulation of Runx2.

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