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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 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], in the present study we observed the effects of 1α,25(OH)2D3 on MT1-MMP expression, and proMMP-2 activation in normal human osteoblast-like cells (hOB). Western immunoblots showed 1α,25(OH)2D3 time and dose dependently stimulated MT1-MMP production. By ELISA, we found that the activation of proMMP-2 in cultures of hOB was intensified by 1α,25(OH)2D3. Our studies suggest that 1α,25(OH)2D3 induces MMP-2 activation in part by up-regulating MT1-MMP expression, and since MT1-MMP plays a role in bone metabolism, the induction of MT1-MMP levels by 1α,25(OH)2D3 in hOB cells may contribute to a new mechanism by which 1α,25(OH)2D3 promotes bone formation and stimulates bone resorption. [ABSTRACT FROM AUTHOR]