Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/90233
Type: Artigo de periódico
Title: Regulation Of Hypoxia-inducible Factor-1α (hif-1α) Expression By Interleukin-1β (il-1β), Insulin-like Growth Factors I (igf-i) And Ii (igf-ii) In Human Osteoarthritic Chondrocytes
Author: Sartori-Cintra A.R.
de Mara C.S.
Argolo D.L.
Coimbra I.B.
Abstract: 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-3- kinase (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. © 2012 CLINICS.
Editor: 
Rights: aberto
Identifier DOI: 10.6061/clinics/2012(01)06
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-84855999133&partnerID=40&md5=7dbdffc315d98739e98bcf6000d33b03
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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