Hypoxia-inducible factor-1α regulates matrix metalloproteinase-1 activity in human bone marrow-derived mesenchymal stem cells

We examined the mRNA levels of hypoxia- inducible factor- 1a ( HIF- 1a) in bone marrow mesenchymal stem cells ( bmMSCs) of eight osteoarthritis patients. BmMSC- 1, expressing higher HIF- 1a mRNA and protein than bmMSC- 5, elicited higher matrix metalloproteinase- 1 ( MMP1) activity and stronger invasive capacity. In vitro invasion assays and quantitative PCR analyses showed that targeted inhibition of HIF- 1a in bmMSC- 1 decreased its invasion and expressions of MMP1 and MMP3, whereas overexpression of HIF- 1a in bmMSC- 5 increased its invasion and expressions of MMP1 and MMP3. Therefore, HIF- 1a can regulate MMP1 and MMP3 expressions in human bmMSCs, which might suggest a pathophysiological role of bmMSC expressing high HIF- 1a in bone diseases. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.