Alendronate stimulates collagenase 3 expression in osteoblasts by posttranscriptional mechanisms.
Bisphosphonates inhibit bone resorption by reducing osteoclastic cell number and activity. Alendronate is a nitrogen-containing bisphosphonate analog used in the treatment of postmenopausal osteoporosis. The effects of alendronate in osteoclasts are well documented; however, there is limited information on the actions of alendronate in osteoblasts (Ob's). In this study, we investigated the effects of alendronate at concentrations of 1-100 microM on the synthesis of collagenase 3 or matrix metalloproteinase 13 (MMP-13) and tissue inhibitors of MMPs (TIMPs) 1, 2, and 3 in primary Ob-enriched cells from 22-day-old fetal rat calvariae. Alendronate at concentrations higher than 10 microM markedly stimulated the synthesis of collagenase messenger RNA (mRNA) and immunoreactive protein in Ob's. Alendronate did not stimulate the transcriptional rate of the collagenase 3 gene. However, in transcriptionally arrested cells, alendronate prolonged the half-life of collagenase transcripts. Alendronate did not alter the expression of TIMP 1 and 2, but modestly stimulated the expression of TIMP 3. The actions of alendronate in Ob's suggest potential additional effects in bone remodeling.
Varghese
S
S
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Canalis
E
E
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000201:enzymology; D002478:Cells, Cultured; D017364:Collagenases / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D053509:Matrix Metalloproteinase 13; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology*; D011480:Protease Inhibitors; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects
D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D019386:Alendronate