Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study used proteomic and transcriptomic techniques to understand the molecular basis of the phenotypic variability in the bone disorder osteogenesis imperfecta (OI). Calvarial bone mRNA expression was evaluated by microarray, real-time, and comparative RT-PCR and the bone proteome profile was analyzed by 2-DE, MS, and immunoblotting in the OI murine model BrtlIV, which has either a moderate or a lethal OI outcome. Differential expression analysis showed significant changes for eight proteins. The expression of the ER stress-related protein Gadd153 was increased in lethal mice, whereas expression of the chaperone alphaB crystallin was increased in nonlethal mice, suggesting that the intracellular machinery is involved in the modulation of the OI phenotype. Furthermore, in lethal BrtlIV, the increased expression of the cartilaginous proteins Prelp, Bmp6, and Bmp7 and the lower expression of the bone matrix proteins matrilin 4, microfibril-associated glycoprotein 2, and thrombospondin 3 revealed that both a delay in skeletal development and an alteration in extracellular matrix composition influence OI outcomes. Differentially expressed proteins identified in this model offer a starting point for elucidating the molecular basis of phenotypic variability, a characteristic common to many genetic disorders. The first reference 2-DE map for murine calvarial tissue is also reported.
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PMID:Differential expression of both extracellular and intracellular proteins is involved in the lethal or nonlethal phenotypic variation of BrtlIV, a murine model for osteogenesis imperfecta. 1752 Jun 86

Diabetic osteoporosis is a metabolic bone disease responsible for global health problems. Hyperglycemia induces osteopenia, increases bone fragility and unbalances the coupling of osteoblasts and osteoclasts. The mechanism is, however, unknown. For the purpose of this study, we hypothesized that hyperglycemia destroys endoplasmic reticulum (ER) homeostasis, activates C/EBP-homologous protein (CHOP) and induces osteoblast apoptosis under diabetic conditions. Diabetic rats were created by injecting streptozotocin (STZ) 65 mg/kg intraperitoneally and their osteoblasts were cultured under high-glucose medium in vitro. The bone mineral density (BMD) and pathological changes of the rats' femurs were observed. The expression of CHOP in osteoblasts was assayed using immunohistochemistry and western blot analysis. Six weeks after diabetic model establishment, a significant decrease was found in the BMD of the diabetic rat femurs, and the numbers of osteoblasts under cortical bone were also reduced. The expression of the ER stress regulator CHOP in osteoblasts of diabetic rats or high-glucose medium was also elevated (P<0.01). The present results demonstrated that hyperglycemia elevated the expression of CHOP and finally led to osteoporosis. This suggested that elevating the expression of CHOP may play a role in diabetic osteoporosis.
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PMID:Hyperglycemia induces endoplasmic reticulum stress-dependent CHOP expression in osteoblasts. 2373 66