Hypoxia-inducible factor-2[alpha] induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells

Objectives To evaluate whether Hypoxia-inducible factor-2[alpha] (HIF-2[alpha]) regulates expression of endochondral ossification-related molecules in human OA meniscus. Methods Expressions of HIF-2[alpha], type X collagen (COL10), matrix metalloproteinase (MMP)-13, and vascular endothelial growth factor (VEGF) in non-OA and OA menisci were analyzed by real-time RT-PCR and immunohistochemistry (IHC). Meniscal cells from OA patients were treated with interleukin-1[beta] (IL-1[beta]) and gene expression was analyzed. After knockdown of HIF-2[alpha] in OA meniscal cells, COL10 and MMP-13 expression were analyzed by RT-PCR, western blotting, immunofluorescence and ELISA. Result Histological analysis demonstrated weak staining of the superficial layer and large round cells in OA meniscus. RT-PCR analysis showed that HIF-2[alpha], COL10, MMP-13, and VEGF mRNA expressions were higher in OA than non-OA meniscal cells. IHC showed a coordinated staining pattern of HIF-2[alpha], COL10, and MMP-13 in OA meniscus. IL-1[beta] treatment increased HIF-2[alpha], COL10, and MMP-13 expressions in OA meniscal cells, and knockdown of HIF-2[alpha] suppressed IL-1[beta]-mediated increase in COL10 and MMP-13 expression. Conclusions These results suggested that HIF-2[alpha] may cause meniscal matrix degradation by transactivation of MMP-13. HIF-2[alpha] may be a therapeutic target for modulating matrix degradation in both articular cartilage and meniscus during knee OA progression.