1alpha,25-dihydroxyvitamin D3 regulates the expression of membrane-type matrix metalloproteinase-1 in normal human osteoblast-like cells.
Recently, membrane-type matrix metalloproteinase-1 (MT1-MMP) was identified, and found that it can activate proMMP-2 on the cell membrane, degrade bone matrix, and participate in bone formation. Since bone is a target tissue of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], in the present study we observed the effects of 1alpha,25(OH)2D3 on MTI-MMP expression, and proMMP-2 activation in normal human ostcoblast-like cells (hOB). Western immunoblots showed 1alpha,25(OH)2D3 time and dose dependently stimulated MTI-MMP production. By ELISA, we found that the activation of proMMP-2 in cultures of hOB was intensified by 1alpha,25(OH)2D3. Our studies suggest that 1alpha,25(OH)2D3 induces MMP-2 activation in part by up-regulating MTI-MMP expression, and since MTI-MMP plays a role in bone metabolism, the induction of MT1-MMP levels by 1alpha,25(OH)2D3 in hOB cells may contribute to a new mechanism by which 1alpha,25(OH)2D3 promotes bone formation and stimulates bone resorption.
Luo
Xiang-hang
XH
Institute of Endocrinology & Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China. xianghangluo@21cn.com
Liao
Er-yuan
EY
D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology
D004792:Enzyme Precursors; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D002117:Calcitriol