title: Influences of diabetes (db/db), obese (ob/ob) and dystrophic (dy/dy) genotype mutations on hind limb bone maturation: a morphometric, radiological and cytochemical indices analysis.
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.
authors: Division of Cell Biology and Biophysics, Schools of Biological Sciences and Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA. garrisd@umkc.edu
authors: D R
authors: DR
authors: Garris
authors: K M
authors: KM
authors: Burkemper
authors: B L
authors: BL
authors: Garris
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D050171:Dyslipidemias / Q000235:genetics*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D005838:Genotype; D006614:Hindlimb; D006615:Hip / Q000000981:diagnostic imaging / Q000473:pathology; D006651:Histocytochemistry / Q000379:methods; D006949:Hyperlipidemias / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009137:Muscular Dystrophy, Animal / Q000000981:diagnostic imaging / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D009765:Obesity / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011859:Radiography; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology