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

Autor(es)

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

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Dept Clin Med, Div Rheumatol, Lab Mol Biol Cartilage, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinics; v. 67, n. 1, p. 35-40, 2012.
• Citações Web of Science: 18

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-1 alpha) 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 alpha in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1 beta) 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 beta, 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 alpha expression was upregulated by IL-1 beta 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 alpha, whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. CONCLUSION: IL-1 beta upregulated the levels of HIF-1 alpha protein post-transcriptionally, whereas IGF-I increased HIF-1a at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1a. 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: 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
• 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