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

Abstract

Objectives: To evaluate whether Hypoxia-inducible factor-2α (HIF-2α) regulates expression of endochondral ossification-related molecules in human OA meniscus.

Methods: Expressions of HIF-2α, 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-1β (IL-1β) and gene expression was analyzed. After knockdown of HIF-2α 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-2α, COL10, MMP-13, and VEGF mRNA expressions were higher in OA than non-OA meniscal cells. IHC showed a coordinated staining pattern of HIF-2α, COL10, and MMP-13 in OA meniscus. IL-1β treatment increased HIF-2α, COL10, and MMP-13 expressions in OA meniscal cells, and knockdown of HIF-2α suppressed IL-1β-mediated increase in COL10 and MMP-13 expression.

Conclusions: These results suggested that HIF-2α may cause meniscal matrix degradation by transactivation of MMP-13. HIF-2α may be a therapeutic target for modulating matrix degradation in both articular cartilage and meniscus during knee OA progression.

Keywords: HIF-2α; Interleukin 1Β; Matrix metalloproteinase 13; Meniscal cell; Osteoarthritis; Type X collagen.