Regulation of hypoxia-inducible factor-1α (HIF-1α) expression by interleukin-1β (IL-1 β), insulin-like growth factors I (IGF-I) and II (IGF-II) in human osteoarthritic chondrocytes

objective: hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. this factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. we hypothesize that hypoxia inducible factor-1 alpha (hif-1α) can regulate cytokines (catabolic action) and/or growth factors (anabolic action) in osteoarthritis. the purpose of this study was to investigate the modulation of hif-1α in human osteoarthritic chondrocytes by interleukin-1 beta (il-1β) and insulin-like growth factors i (igf-i) and ii (igf-ii) and to determine the involvement of the phosphatidylinositol-3kinase (pi-3k) pathway in this process. methods: human osteroarthritic chondrocytes were stimulated with il-1β, igf-i and igf-ii and ly294002, a specific inhibitor of pi-3k. nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. results: hif-1α expression was upregulated by il-1β at the protein level but not at the gene level. igf-i treatment resulted in increases in both the protein and mrna levels of hif-1α , whereas igf-ii had no effect on its expression. however, all of these stimuli exploited the pi-3k pathway. conclusion: il-1β upregulated the levels of hif-1α protein post-transcriptionally, whereas igf-i increased hif-1α at the transcript level. in contrast, igf-ii did not affect the protein or gene expression levels of hif-1α . furthermore, all of the tested stimuli exploited the pi-3k pathway to some degree. based on these findings, we are able to suggest that hypoxia inducible factor-1 exhibits protective activity in chondrocytes during osteoarthritis.