軟骨変性機序における低酸素環境適応因子 hypoxia inducible factor (HIF)-1α の発現と二次的防御因子としての役割

概要

論文の詳細を見る
Objective: To study the role of the transcription factor hypoxia inducible factor (HIF)-1α in chondrocyte viability as a cell survival factor during the progression of OA. Methods: The expression of HIF-1α was histologically investigated in human OA cartilage samples. We studied whether IL-1β induces the expression of HIF-1α in OA chondrocytes under normoxic and hypoxic conditions. Also, we examined the levels of energy generation, and cartilage-matrix production in HIF-1α-deficient chondrocytes.Results: In articular cartilages from human OA patients, the amount of HIF-1α correlated with the degree of cartilage degeneration. IL-1β up-regulated mRNA and protein levels of HIF-1α in cultured chondrocytes. HIF-1α-deficient chondrocytes did not maintain the energy generation under both normoxic and hypoxic conditions. HIF-1α-deficient chondrocytes showed an acceleration of catabolic stress-induced apoptosis.Conclusion: Our results in human OA cartilage and in an OA rat model suggest that HIF-1α expression in OA cartilage is closely associated with the progression of articular cartilage degeneration. Catabolic-stresses may accelerate the HIF-1α expression in chondrocytes, suggesting an important role for HIF-1α in the chondrocyte activity in OA articular cartilage.
日本炎症・再生医学会の論文
2005-05-25