[The effects of 1alpha,25-dihydroxyvitamin D3 in regulation matrix metalloproteinase and tissue metalloproteinase inhibitors in human osteoblasts].
OBJECTIVE
To characterize the effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] on the expression of matrix metalloproteinase (MMP)-1, MMP-2, membrane-type MMP-1 (MT1-MMP), tissue inhibitors of metalloproteinase-1 (TIMP-1) in human osteoblast, and understand the mechanism by which 1alpha,25(OH)2D3 exert on bone.


METHODS
Osteoblasts were interfered by 1alpha,25(OH2D3. Western blot were used to show the action of 1alpha,25(OH)2D3 on the expression of MT1-MMP protein in human osteoblasts. ELISA was done to examine the effect of 1alpha,25(OH)2D3 on the activity of MMP-2. Northern blot analysis was performed to detect vitamin D receptor mRNA levels and to evaluate the effect of 1alpha,25(OH)2D3 on MT1-MMP mRNA levels.


RESULTS
The results showed that 1alpha,25(OH)2D3 had no effect on the expression of MMP-1, MMP-2 and TIMP-1 in human osteoblasts; 10(-10) - 10(-8) mol/L 1alpha,25(OH)2D3 induced MT1-MMP expression in a dose-dependent manner (P < 0.05), 10(-10) - 10(-8) mol/L 1alpha,25(OH)2D3 induced the activation of proMMP-2 in a dose-dependent manner in human osteoblasts[The activity of MMP-2 was (42.3 +/- 8.6), (64.4 +/- 11.4), (93.5 +/- 9.9) microg/L respectively, P < 0.05].


CONCLUSIONS
1alpha,25(OH)2D3 may stimulate bone resorption by inducing MT1-MMP production in osteoblasts.
Guo
Li-juan
LJ
Institute of Endocrinology & Metabolism, the Second Xiangya Hospital of Central South Medical University, Changsha 410011, China.
Luo
Xiang-hang
XH
Xie
Hui
H
Zhou
Hou-de
HD
Liao
Er-yuan
EY
D000328:Adult; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D018167:Receptors, Calcitriol; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D002117:Calcitriol