%0 Journal Article
%T Regulation of hypoxia-inducible factor-1¦Á (HIF-1¦Á) expression by interleukin-1¦Â (IL-1 ¦Â), insulin-like growth factors I (IGF-I) and II (IGF-II) in human osteoarthritic chondrocytes
%A Sartori-Cintra
%A Angelica Rossi
%A Mara
%A Cristiane Sampaio de
%A Argolo
%A Danielle L
%A Coimbra
%A Ibsen Bellini
%J Clinics
%D 2012
%I Faculdade de Medicina / USP
%R 10.6061/clinics/2012(01)06
%X 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-1¦Á) 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-1¦Á in human osteoarthritic chondrocytes by interleukin-1 beta (il-1¦Â) 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-1¦Â, 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-1¦Á expression was upregulated by il-1¦Â 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-1¦Á , whereas igf-ii had no effect on its expression. however, all of these stimuli exploited the pi-3k pathway. conclusion: il-1¦Â upregulated the levels of hif-1¦Á protein post-transcriptionally, whereas igf-i increased hif-1¦Á at the transcript level. in contrast, igf-ii did not affect the protein or gene expression levels of hif-1¦Á . 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.
%K hif-1¦Á
%K chondrocytes
%K phosphatidylinositol-3-kinase (pi-3k)
%K cytokines
%K il-1¦Â
%K growth factors
%K igf-i
%K igf-ii
%K osteoarthritis
%K articular cartilage.
%U http://www.scielo.br/scielo.php?script=sci_abstract&pid=S1807-59322012000100006&lng=en&nrm=iso&tlng=en