PMID- 11127199
OWN - NLM
STAT- MEDLINE
DCOM- 20010201
LR  - 20131121
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 15
IP  - 12
DP  - 2000 Dec
TI  - Alendronate stimulates collagenase 3 expression in osteoblasts by 
      posttranscriptional mechanisms.
PG  - 2345-51
AB  - 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.
FAU - Varghese, S
AU  - Varghese S
AD  - Department of Research, Saint Francis Hospital and Medical Center, Hartford, 
      Connecticut 06105, USA.
FAU - Canalis, E
AU  - Canalis E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Protease Inhibitors)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Mmp13 protein, rat)
RN  - X1J18R4W8P (Alendronate)
SB  - IM
MH  - Alendronate/*pharmacology
MH  - Animals
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Bone Remodeling/drug effects
MH  - Bone Resorption/*drug therapy/enzymology
MH  - Cells, Cultured
MH  - Collagenases/*drug effects
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Matrix Metalloproteinase 13
MH  - Osteoblasts/*drug effects/*enzymology
MH  - Protease Inhibitors
MH  - Rats
MH  - Tissue Inhibitor of Metalloproteinases/drug effects
EDAT- 2000/12/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/29 11:00
PHST- 2000/12/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/29 11:00 [entrez]
AID - 10.1359/jbmr.2000.15.12.2345 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2000 Dec;15(12):2345-51. doi: 10.1359/jbmr.2000.15.12.2345.