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Publication : Expression profiles of mRNAs for osteoblast and osteoclast proteins as indicators of bone loss in mouse immobilization osteopenia model.

First Author  Rantakokko J Year  1999
Journal  J Bone Miner Res Volume  14
Issue  11 Pages  1934-42
PubMed ID  10571694 Mgi Jnum  J:61034
Mgi Id  MGI:1354251 Doi  10.1359/jbmr.1999.14.11.1934
Citation  Rantakokko J, et al. (1999) Expression profiles of mRNAs for osteoblast and osteoclast proteins as indicators of bone loss in mouse immobilization osteopenia model. J Bone Miner Res 14(11):1934-42
abstractText  An experimental mouse model for disuse osteopenia was developed using unilateral cast immobilization. Analysis of the distal femurs and proximal tibias by quantitative histomorphometry revealed significant osteopenia within 10-21 days of immobilization. At 3 weeks, bone loss was also demonstrated with peripheral quantitative computed tomography as diminished bone mineral content and as concomitant reduction in the cross-sectional moment of inertia. These structural and geometrical alterations resulted in decreased strength of the distal femurs tested by cantilever bending. Analysis of the underlying cellular and molecular mechanisms of bone loss revealed a rapid increase in bone resorption within 3 days of immobilization. The mRNA levels for cathepsin K, matrix metalloproteinase-9, and tartrate resistant acid phosphatase were all significantly increased during the 21-day immobilization period, but with different expression profiles. These increases were paralleled by an increased number of osteoclasts as measured by histomorphometry. By day 6 of immobilization, the balance of bone turnover was further shifted toward net bone loss as the mRNA levels for major bone components (type I collagen and osteocalcin) were decreased. In histomorphometric analysis this was observed as reduced rates of mineral apposition and bone formation after 10 days of immobilization. The results of this study demonstrate that immobilization has a dual negative effect on bone turnover involving both depressed bone formation and enhanced bone resorption.
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