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 proteolyt...
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| Format: | Article |
| Language: | English |
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Elsevier España
2012-01-01
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| Series: | Clinics |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322012000100006 |
| _version_ | 1811229282420129792 |
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| author | Angelica Rossi Sartori-Cintra Cristiane Sampaio de Mara Danielle L Argolo Ibsen Bellini Coimbra |
| author_facet | Angelica Rossi Sartori-Cintra Cristiane Sampaio de Mara Danielle L Argolo Ibsen Bellini Coimbra |
| author_sort | Angelica Rossi Sartori-Cintra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T10:13:13Z |
| format | Article |
| id | doaj.art-1f3e76a7df524067a00f0078b11f9a4d |
| institution | Directory Open Access Journal |
| issn | 1807-5932 1980-5322 |
| language | English |
| last_indexed | 2024-04-12T10:13:13Z |
| publishDate | 2012-01-01 |
| publisher | Elsevier España |
| record_format | Article |
| series | Clinics |
| spelling | doaj.art-1f3e76a7df524067a00f0078b11f9a4d2022-12-22T03:37:16ZengElsevier EspañaClinics1807-59321980-53222012-01-01671354010.1590/S1807-59322012000100006Regulation 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 chondrocytesAngelica Rossi Sartori-CintraCristiane Sampaio de MaraDanielle L ArgoloIbsen Bellini CoimbraOBJECTIVE: 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322012000100006HIF-1αChondrocytesPhosphatidylinositol-3-kinase (PI-3K), CytokinesIL-1βGrowth factorsIGF-I, IGF-II, OsteoarthritisArticular cartilage |
| spellingShingle | Angelica Rossi Sartori-Cintra Cristiane Sampaio de Mara Danielle L Argolo Ibsen Bellini Coimbra 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 Clinics HIF-1α Chondrocytes Phosphatidylinositol-3-kinase (PI-3K), Cytokines IL-1β Growth factors IGF-I, IGF-II, Osteoarthritis Articular cartilage |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | regulation of hypoxia inducible factor 1 945 hif 1 945 expression by interleukin 1 946 il 1 946 insulin like growth factors i igf i and ii igf ii in human osteoarthritic chondrocytes |
| topic | HIF-1α Chondrocytes Phosphatidylinositol-3-kinase (PI-3K), Cytokines IL-1β Growth factors IGF-I, IGF-II, Osteoarthritis Articular cartilage |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322012000100006 |
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