Effect of low dietary calcium on bone metabolism in the SENCAR mouse.
The SENCAR (sensitive to carcinogenesis) mouse is a unique tool for investigating the interaction between a specific defect in intracellular signaling, dietary calcium, and metabolic bone disease. The SENCAR mouse was developed by selective breeding for enhanced sensitivity to two-stage carcinogenesis. Its major genetic defect, which renders it exquisitely sensitive to stimulation with diacylglycerol or phorbol esters, is in the regulatory domain of protein kinase C, one of the primary intracellular mediators of hormonal effects. At sexual maturity, SENCAR mice are large and have big bones, but our previous pharmacokinetic studies showed that they accumulate less calcium under normal conditions and lose more calcium under adverse conditions than do other, standard strains of mice. To histologically define the effect of low dietary calcium on bone metabolism, we performed histomorphometric analysis of tetracycline-labeled sections of femoral bone from male SENCAR mice maintained on calcium-sufficient and calcium-deficient diets during the critical period from 10 to 14 weeks of age. The bone volume, absolute osteoid volume, and mineral apposition rate were lower at 14 than at 10 weeks of age in SENCAR mice fed 0.02 or 0.6% calcium diets. Calcium deficiency increased the architectural disarray and the probability of observing focal discontinuities in the growth plate. Thus, characteristic features of impaired bone metabolism (low bone volume and apposition rate) develop early in SENCAR mice and are exacerbated by low dietary calcium. Detailed examinations of the histology and biochemistry of SENCAR mouse bone will provide insights into the mechanisms by which specific defects in the signal transduction of protein kinase C contribute to impaired bone metabolism.
Murray
E J
EJ
Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Sepulveda, CA 91343, USA. murrayes@ucla.edu
Murray
S S
SS
Grisanti
M
M
Duarte
M E
ME
Urist
M R
MR
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000502:physiology*; D002118:Calcium / Q000172:deficiency*; D002136:Calcium, Dietary / Q000493:pharmacokinetics*; D006132:Growth Plate / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018632:Mice, Inbred SENCAR
D002136:Calcium, Dietary; D002118:Calcium