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Previously, we showed that hypoxia and its mediator HIF\u20101 regulate matrix genes expression (collagens and aggrecan). Here, we investigated the molecular mechanism involved in the regulation of type I collagen (COL1A1) by HIF\u20101 in human articular chondrocytes. We show that HIF\u20101\u03b1 reduces COL1A1 transcription, through a distal promoter (\u22122300 to \u22121816 bp upstream transcription initiation site), containing two GC boxes that bind Sp transcription factors (Sp1\/Sp3). Sp1 acts as a positive regulator but is not induced by HIF\u20101. COL1A1 inhibition caused by HIF\u20101 implies only Sp3, which accumulates and competes Sp1 binding on COL1A1 promoter. Additionally, Sp3 ectopic expression inhibits COL1A1, while Sp3 knockdown counteracts the downregulation of COL1A1 induced by HIF\u20101. In conclusion, we established a new regulatory model of COL1A1 regulation by HIF\u20101, and bring out its relationship with Sp3 transcription factor. In a fundamental level, these findings give insights in the mechanisms controlling COL1A1 gene expression. This may be helpful to improve strategies to impair type I collagen expression during chondrocyte differentiation for cartilage engineering. \u00a9 2016 IUBMB Life, 68(9):756\u2013763, 2016<\/jats:p>","DOI":"10.1002\/iub.1539","type":"journal-article","created":{"date-parts":[[2016,8,13]],"date-time":"2016-08-13T06:32:43Z","timestamp":1471069963000},"page":"756-763","source":"Crossref","is-referenced-by-count":24,"title":["Hypoxia inducible factor 1 alpha down\u2010regulates type i collagen through Sp3 transcription factor in human chondrocytes"],"prefix":"10.1002","volume":"68","author":[{"given":"Elise","family":"Duval","sequence":"first","affiliation":[{"name":"EA4652, Equipe BioConnecT, UNICAEN Caen CS 14032 France"},{"name":"Normandie University, UFR de m\u00e9decine Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouloud","family":"Bouyoucef","sequence":"additional","affiliation":[{"name":"EA4652, Equipe BioConnecT, UNICAEN Caen CS 14032 France"},{"name":"Normandie University, UFR de m\u00e9decine Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Leclercq","sequence":"additional","affiliation":[{"name":"EA4652, Equipe BioConnecT, UNICAEN Caen CS 14032 France"},{"name":"Normandie University, UFR de m\u00e9decine Caen France"},{"name":"D\u00e9partement De Chirurgie Orthop\u00e9dique Clinique Saint\u2010Martin Caen 14000 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Baug\u00e9","sequence":"additional","affiliation":[{"name":"EA4652, Equipe BioConnecT, UNICAEN Caen CS 14032 France"},{"name":"Normandie University, UFR de m\u00e9decine Caen France"},{"name":"F\u00e9d\u00e9ration Hospitalo Universitaire SURFACE, Amiens, Rouen, Caen  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Boum\u00e9diene","sequence":"additional","affiliation":[{"name":"EA4652, Equipe BioConnecT, UNICAEN Caen CS 14032 France"},{"name":"Normandie University, UFR de m\u00e9decine Caen France"},{"name":"F\u00e9d\u00e9ration Hospitalo Universitaire SURFACE, Amiens, Rouen, Caen  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/438026"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24851"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.04.061"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"14385","DOI":"10.1016\/S0021-9258(17)43873-7","article-title":"The mRNAs for the pro\u2010alpha 1(I) and pro\u2010alpha 2(I) chains of type I procollagen are translated at the same rate in normal human fibroblasts and in fibroblasts from two variants of osteogenesis imperfecta with altered steady state ratios of the two mRNAs","volume":"258","author":"Wet W. 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