HIF2A: mastering osteoarthritis

Most approved osteoarthritis therapies treat symptoms of the disease but not the underlying processes that lead to cartilage destruction and bone spur formation in joints. Now, separate research teams from Japan and South Korea have shown that the transcription factor endothelial PAS domain protein 1 is a key regulator of osteoarthritis pathogenesis.1,2

Both teams expect that endothelial PAS domain protein 1 (EPAS1; HIF2A) inhibitors could treat or prevent the disease, although the researchers differ on whether HIF2A itself or an upstream activator of the transcription factor would be a better drug target.

The normal growth of long bones and the development of OA both depend on endochondral ossification, a process that involves the growth, expansion and subsequent degradation of cartilage cells. However, the molecular factors that regulate and coordinate the process-including what goes awry in OA-are not well understood.

HIF2A is a member of the family of hypoxia-inducible factors (HIFs) that are activated under hypoxic conditions. Although cartilage

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