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Diabetes Obes Metab ; 9(3): 311-22, 2007 May.
Article in English | MEDLINE | ID: mdl-17391157

ABSTRACT

The influences of single-gene missense mutations expressing diabetes (db/db), obese (ob/ob) or dystrophia (dy/dy) dysregulated metabolic syndromes on hind limb bone maturation and cytodevelopment in C57BL/KsJ mice were evaluated by radiological, macro- and cytomorphometric analysis of the resulting variances in os coxae, femur and tibia osteodevelopment indices relative to control parameters between 8 and 16 weeks of age. Associated with obesity and hyperglycaemic/hyperinsulinaemic states, both db/db and ob/ob mutants demonstrated significant suppression of hind limb maturation (length) and cytodensity indices relative to control growth parameters. By contrast, skeletal growth suppression induced by dy/dy mutation expression was associated with lean body mass and normoglycaemic/hypoinsulinaemic systemic endometabolic indices. In both db/db and ob/ob mutation syndromes, osteovascular, -interstitial and -cytolipidaemia were prominent cytochemical aberrations of the osteopaenic states relative to the dyslipidaemia/fibrodysplasia characteristic of dy/dy osteomaturation. Between 8 and 16 weeks of age, both ob/ob and db/db groups demonstrated extensive cortical interstitial (laminal) osteolipidaemia and suppressed cytodensities compared to control indices. These data demonstrate that the abnormal hyperglycaemic/hyperinsulinaemic endometabolic states associated with the expression of db/db and ob/ob genomutations promote extensive lipidaemia-induced osteopaenia, compromising hind limb osteomaturation and cytodensity indices, as compared to the hyperfibritic osteopaenia characteristic of dy/dy mutation syndromes. Recognized therapeutic modulation of the hypercytolipidaemic component of diabetes-obesity syndromes may prove to be effective towards amelioration of the deleterious influences of these expressed hyperglycaemic, dysregulated lipometabolic conditions on osteomaturation and cytodevelopment.


Subject(s)
Bone Development/genetics , Diabetes Mellitus, Experimental/genetics , Dyslipidemias/genetics , Muscular Dystrophy, Animal/genetics , Mutation, Missense/genetics , Obesity/genetics , Animals , Diabetes Mellitus, Experimental/diagnostic imaging , Diabetes Mellitus, Experimental/pathology , Female , Femur/diagnostic imaging , Femur/pathology , Genotype , Hindlimb , Hip/diagnostic imaging , Hip/pathology , Histocytochemistry/methods , Hyperlipidemias/genetics , Mice , Mice, Inbred C57BL , Muscular Dystrophy, Animal/diagnostic imaging , Obesity/diagnostic imaging , Obesity/pathology , Radiography , Tibia/diagnostic imaging , Tibia/pathology
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