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

We examined the mRNA levels of hypoxia-inducible factor-1alpha (HIF-1alpha) in bone marrow mesenchymal stem cells (bmMSCs) of eight osteoarthritis patients. BmMSC-1, expressing higher HIF-1alpha 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-1alpha in bmMSC-1 decreased its invasion and expressions of MMP1 and MMP3, whereas overexpression of HIF-1alpha in bmMSC-5 increased its invasion and expressions of MMP1 and MMP3. Therefore, HIF-1alpha can regulate MMP1 and MMP3 expressions in human bmMSCs, which might suggest a pathophysiological role of bmMSC expressing high HIF-1alpha in bone diseases.