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.
Lin
Jiunn-Liang
JL
Orthopaedics Medicine, Miaoli General Hospital, Miaoli city, Taiwan.
Wang
Ming Jen
MJ
Lee
Donching
D
Liang
Chun-Chin
CC
Lin
Shankung
S
D000368:Aged; D001853:Bone Marrow / Q000201:enzymology; D002478:Cells, Cultured; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D010003:Osteoarthritis / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1