HIF pathway-mediated regulation of OC progenitor cells. Under hypoxic conditions, the HIF complex binds to its response elements (HREs) on target genes (A) where it acts to enhance SOX9 expression and activity (B), resulting in increased production of cartilage ECM (C), dampened activity of RUNX2
(D), and reduced expression of genes involved in osteogenesis (E) and chondrocyte hypertrophy (F). HIF has also been shown to increase expression of glycolytic enzymes (G) as well as Wnt antagonists involved in delaying chondrocyte hypertrophy (H). Yellow arrows indicate pathways/genes that are activated, while red arrows show pathways/genes that are inhibited under hypoxic conditions. ECM, extracellular matrix; HIF, hypoxia inducible factor; HRE, hypoxia-responsive element; OC, osteochondral. Color images are available online.