Prostaglandin E2 increases the skeletal response to mechanical loading

The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combi...

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Bibliographic Details
Published in:Journal of bone and mineral research 1997-02, Vol.12 (2), p.276-282
Main Authors: Tang, L. Y., Cullen, D. M., Yee, J. A., Jee, W. S., Kimmel, D. B.
Format: Article
Language:English
Subjects:
Aerospace Medicine
Animals
Biological and medical sciences
Bone and Bones - drug effects
Bone and Bones - metabolism
Bone and Bones - physiology
Dinoprostone - pharmacology
Dinoprostone - physiology
Dose-Response Relationship, Drug
Female
Fundamental and applied biological sciences. Psychology
Osteogenesis - drug effects
Osteogenesis - physiology
Rats
Rats, Sprague-Dawley
Skeleton and joints
Space life sciences
Stress, Mechanical
Tibia - drug effects
Tibia - physiology
Vertebrates: osteoarticular system, musculoskeletal system
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Summary:The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.
ISSN:0884-0431
1523-4681
DOI:10.1359/jbmr.1997.12.2.276