HIF-1alpha controls extracellular matrix synthesis by epiphyseal chondrocytes
- PMID: 12665562
- DOI: 10.1242/jcs.00385
HIF-1alpha controls extracellular matrix synthesis by epiphyseal chondrocytes
Abstract
The transcription factor HIF-1alpha plays a crucial role in modifying gene expression during low oxygen tension. In a previous study, we demonstrated that HIF-1alpha is essential for chondrocyte growth arrest and survival in vivo. To explore further the role of HIF-1alpha in cartilage biology, we undertook studies with primary epiphyseal chondrocytes with a targeted deletion of HIF-1alpha. In this study, we show that HIF-1alpha is necessary for regulating glycolysis under aerobic and anaerobic conditions. HIF-1alpha-null chondrocytes were unable to maintain ATP levels in hypoxic microenvironments, indicating a fundamental requirement for this factor for the regulation of chondrocyte metabolism. Synthesis of the angiogenic factor vascular endothelial growth factor was also significantly induced by hypoxia, and this increase is lost in HIF-1alpha-null mutant cells. Under hypoxic conditions, aggrecan mRNA and protein levels were significantly reduced in chondrocytes lacking the HIF-1alpha transcription factor. Interestingly, strongly increased type-II collagen protein levels were detected in wild-type cells after 44 hours of hypoxia. In addition, type-II collagen mRNA and protein levels were strongly decreased under low oxygen in chondrocytes lacking HIF-1alpha. In summary, our results clearly demonstrate the importance of HIF-1alpha in maintenance of anaerobic glycolysis, and thereby extracellular matrix synthesis, of epiphyseal chondrocytes.
Similar articles
-
Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.PLoS One. 2016 Feb 3;11(2):e0148372. doi: 10.1371/journal.pone.0148372. eCollection 2016. PLoS One. 2016. PMID: 26841115 Free PMC article.
-
VEGF-independent cell-autonomous functions of HIF-1α regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival.J Bone Miner Res. 2012 Mar;27(3):596-609. doi: 10.1002/jbmr.1487. J Bone Miner Res. 2012. PMID: 22162090
-
Hypoxia-inducible factor 1alpha inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1alpha-dependent redifferentiation of chondrocytes.Arthritis Rheum. 2009 Oct;60(10):3038-48. doi: 10.1002/art.24851. Arthritis Rheum. 2009. PMID: 19790048
-
Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments.Curr Opin Rheumatol. 2007 Sep;19(5):457-62. doi: 10.1097/BOR.0b013e3282ba5693. Curr Opin Rheumatol. 2007. PMID: 17762611 Review.
-
Fetal growth plate: a developmental model of cellular adaptation to hypoxia.Ann N Y Acad Sci. 2007 Nov;1117:26-39. doi: 10.1196/annals.1402.076. Ann N Y Acad Sci. 2007. PMID: 18056035 Review.
Cited by
-
Knockdown of hypoxia-inducible factor-1α accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines.Exp Ther Med. 2012 Sep;4(3):355-362. doi: 10.3892/etm.2012.600. Epub 2012 Jun 6. Exp Ther Med. 2012. PMID: 23181099 Free PMC article.
-
Expression and significance of related genes in the early stage of post-traumatic heterotopic ossification in a rat model of Achilles tenotomy.Acta Orthop Traumatol Turc. 2021 Mar;55(2):94-101. doi: 10.5152/j.aott.2021.18480. Acta Orthop Traumatol Turc. 2021. PMID: 33847569 Free PMC article.
-
Hypoxia-Inducible Factor (HIF) as a Target for Novel Therapies in Rheumatoid Arthritis.Front Pharmacol. 2016 Jun 27;7:184. doi: 10.3389/fphar.2016.00184. eCollection 2016. Front Pharmacol. 2016. PMID: 27445820 Free PMC article. Review.
-
Regulation of VEGF expression by HIF-1α in the femoral head cartilage following ischemia osteonecrosis.Sci Rep. 2012;2:650. doi: 10.1038/srep00650. Epub 2012 Sep 11. Sci Rep. 2012. PMID: 22970342 Free PMC article.
-
Hypoxia-driven pathways in bone development, regeneration and disease.Nat Rev Rheumatol. 2012 Mar 27;8(6):358-66. doi: 10.1038/nrrheum.2012.36. Nat Rev Rheumatol. 2012. PMID: 22450551 Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources