PMID- 21498965 OWN - NLM STAT- MEDLINE DCOM- 20110902 LR - 20190727 IS - 1349-3329 (Electronic) IS - 0040-8727 (Linking) VI - 224 IP - 1 DP - 2011 May TI - Hypoxia induces osteogenesis-related activities and expression of core binding factor alpha1 in mesenchymal stem cells. PG - 7-12 AB - 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-1alpha) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfalpha1) 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-1alpha and Cbfalpha1 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 Cbfalpha1 mRNA after 12 h, whereas the expression of HIF-1alpha mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1alpha expression with a small interfering RNA significantly increased the expression levels of Cbfalpha1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfalpha1 may be negatively regulated by HIF-1alpha. FAU - Huang, Jiao AU - Huang J AD - Department of Periodontology, Affiliated Hospital of Stomatology, Chongqing University of Medical Sciences, PR China. FAU - Deng, Feng AU - Deng F FAU - Wang, Lu AU - Wang L FAU - Xiang, Xue-Rong AU - Xiang XR FAU - Zhou, Wen-Wen AU - Zhou WW FAU - Hu, Na AU - Hu N FAU - Xu, Ling AU - Xu L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Tohoku J Exp Med JT - The Tohoku journal of experimental medicine JID - 0417355 RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Cell Hypoxia/genetics/physiology MH - Cell Proliferation MH - Core Binding Factor Alpha 1 Subunit/genetics/*metabolism MH - Gene Expression Regulation MH - Gene Knockdown Techniques MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism MH - Male MH - Mesenchymal Stem Cells/cytology/*metabolism MH - *Osteogenesis/genetics MH - RNA, Messenger/genetics/metabolism MH - Rabbits EDAT- 2011/04/19 06:00 MHDA- 2011/09/03 06:00 CRDT- 2011/04/19 06:00 PHST- 2011/04/19 06:00 [entrez] PHST- 2011/04/19 06:00 [pubmed] PHST- 2011/09/03 06:00 [medline] AID - JST.JSTAGE/tjem/224.7 [pii] AID - 10.1620/tjem.224.7 [doi] PST - ppublish SO - Tohoku J Exp Med. 2011 May;224(1):7-12. doi: 10.1620/tjem.224.7.