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

Autor(es)

Angelica Rossi Sartori-Cintra ^[1] ; Cristiane Sampaio de Mara ^[2] ; Danielle L Argolo ^[3] ; Ibsen Bellini Coimbra ^[4]

Afiliação do(s) autor(es)

^[1] State University of Campinas. Department of Clinical Medicine. Division of Rheumatology Laboratory of Molecular Biology of Cartilage - Brasil

^[2] State University of Campinas. Department of Clinical Medicine. Division of Rheumatology Laboratory of Molecular Biology of Cartilage - Brasil

^[3] State University of Campinas. Department of Clinical Medicine. Division of Rheumatology Laboratory of Molecular Biology of Cartilage - Brasil

^[4] State University of Campinas. Department of Clinical Medicine. Division of Rheumatology Laboratory of Molecular Biology of Cartilage - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 67, n. 1, p. 35-40, 2012-00-00.

Resumo

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. (AU)

• Processo FAPESP: 02/14132-1 - Estudo da expressão do HIF-1 (fator induzido por hipoxia-1) em condrócitos articulares, humanos normais e em osteoartrite tratados com interleucina-1 beta, fator de necrose tumoral-alfa e fatores de crescimento insulina-like
• Beneficiário: Ibsen Bellini Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/00985-0 - Participação do HIF-1 alpha na expressão de colágeno Tipo II e agrecanos na cartilagem articular sob condições de hipóxia e normóxia mediada por IL-1 beta e TNF-alpha
• Beneficiário: Angélica Rossi Sartori
• Modalidade de apoio: Bolsas no Brasil - Doutorado