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
;
67(1): 35-40, 2012. ilus
Article
Dans Anglais
| LILACS
| ID: lil-610621
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-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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Arthrose
/
Facteur de croissance IGF-I
/
Facteur de croissance IGF-II
/
Régulation de l'expression des gènes
/
Chondrocytes
/
Sous-unité alpha du facteur-1 induit par l'hypoxie
/
Interleukine-1 bêta
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Clinics
Thème du journal:
Médicament
Année:
2012
Type:
Article
/
descriptif de projet
Pays d'affiliation:
Brésil
Institution/Pays d'affiliation:
State University of Campinas/BR
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS