Alendronate stimulates collagenase 3 expression in osteoblasts by posttranscriptional mechanisms

Bisphosphonates inhibit bone resorption by reducing osteoclastic cell numbe r and activity. Alendronate is a nitrogen-containing bisphosphonate analog used in the treatment of postmenopausal. osteoporosis. The effects of alend ronate in osteoclasts are well documented; however, there is limited inform ation on the actions of alendronate in osteoblasts (Ob's), In this study, w e investigated the effects of alendronate at concentrations of 1-100 muM 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 muM markedly stimulated the synthesis of collagenase messenger RNA (mRNA) and immunoreactive protein in Ob's, Alendronate did not stimulate th e transcriptional rate of the collagenase 3 gene. However, in transcription ally arrested cells, alendronate prolonged the half-life of collagenase tra nscripts. Alendronate did not alter the expression of TIMP 1 and 2, but mod estly stimulated the expression of TIMP 3, The actions of alendronate in Ob 's suggest potential additional effects in bone remodeling.