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].
Conclusion: 1alpha,25(OH)2D3 may stimulate bone resorption by inducing MT1-MMP production in osteoblasts.