title: Hypoxia induces osteogenesis-related activities and expression of core binding factor α1 in mesenchymal stem cells.
abstract: Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO(2)) or hypoxia (5% CO(2) and 95% N(2)). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.
authors.affiliation: Department of Periodontology, Affiliated Hospital of Stomatology, Chongqing University of Medical Sciences, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Deng
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Xue-Rong
authors.initials: XR
authors.lastname: Xiang
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Zhou
authors.forename: Na
authors.initials: N
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger