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

Abstract 

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

Abbreviations: HIF-1α, hypoxia-inducible factor-1α, siRNA, small interfering RNA, GFP, green fluorescence protein, MMP, matrix metalloproteinase, APMA, p-aminophenylmercuric acetate

Keywords: Hypoxia-inducible factor-1α, Osteoarthritis, Bone marrow mesenchymal stem cells, Matrix metalloproteinase-1