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Alendronate Stimulates Collagenase 3 Expression in Osteoblasts by Posttranscriptional Mechanisms
Author(s) -
Varghese Samuel,
Canalis Ernesto
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.12.2345
Subject(s) - collagenase , interstitial collagenase , bisphosphonate , endocrinology , medicine , bone resorption , matrix metalloproteinase , osteoporosis , bone remodeling , osteoblast , chemistry , resorption , messenger rna , bone cell , mmp1 , alendronic acid , gene expression , biology , enzyme , in vitro , biochemistry , gene
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 μM 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 μM 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.