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000285487 1001_ $$aÖzkan, Burak$$b0
000285487 245__ $$aReduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model.
000285487 260__ $$aAnn Arbor, Michigan$$bJCI Insight$$c2026
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000285487 520__ $$aAmyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Emerging evidence suggests manifestations beyond the neuromuscular system. Bone alterations are part of the ALS clinical picture; it remains unclear whether they are secondary to muscle denervation or due to an autonomous process. We investigated skeletal involvement in the SOD1(G93A) mouse model at presymptomatic (P45) and symptomatic (P110) stages through biomechanical and transcriptomic approaches. Three-point bending revealed significant reductions in femoral rigidity and maximum bending force in SOD1 mutants at P45, indicating early structural deficits. Micro-CT analysis demonstrated reduced trabecular bone mineral density and thickness at P45, with progressive trabecular loss and cortical thinning by P110. Histological examination revealed marked osteoblast loss at P45, suggesting impaired bone formation as the primary early mechanism. Transcriptomics of bulk bone and cultured osteoblasts from P45 mice identified dysregulation of bone differentiation, including downregulation of osteoblast differentiation genes and upregulation of negative regulators of ossification and increased cell senescence signatures. Unfolded protein response was upregulated in SOD1 osteoblasts. Immunohistochemistry confirmed the senescence phenotype with increased p16Ink4a level in SOD1 osteoblasts. These findings suggest that bone deterioration precedes overt motor symptoms and is linked to osteoblast premature senescence.
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000285487 650_7 $$2Other$$aBone biology
000285487 650_7 $$2Other$$aCell biology
000285487 650_7 $$2Other$$aCellular senescence
000285487 650_7 $$2Other$$aNeurodegeneration
000285487 650_7 $$2Other$$aNeuroscience
000285487 650_7 $$2Other$$aOsteoclast/osteoblast biology
000285487 650_7 $$0EC 1.15.1.1$$2NLM Chemicals$$aSuperoxide Dismutase-1
000285487 650_7 $$0EC 1.15.1.1$$2NLM Chemicals$$aSOD1 G93A protein
000285487 650_7 $$0EC 1.15.1.1$$2NLM Chemicals$$aSod1 protein, mouse
000285487 650_7 $$0EC 1.15.1.1$$2NLM Chemicals$$aSuperoxide Dismutase
000285487 650_2 $$2MeSH$$aAnimals
000285487 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: genetics
000285487 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: pathology
000285487 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: metabolism
000285487 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: physiopathology
000285487 650_2 $$2MeSH$$aOsteoblasts: metabolism
000285487 650_2 $$2MeSH$$aOsteoblasts: pathology
000285487 650_2 $$2MeSH$$aDisease Models, Animal
000285487 650_2 $$2MeSH$$aMice
000285487 650_2 $$2MeSH$$aSuperoxide Dismutase-1: genetics
000285487 650_2 $$2MeSH$$aSuperoxide Dismutase-1: metabolism
000285487 650_2 $$2MeSH$$aOsteogenesis: genetics
000285487 650_2 $$2MeSH$$aMice, Transgenic
000285487 650_2 $$2MeSH$$aCellular Senescence: genetics
000285487 650_2 $$2MeSH$$aX-Ray Microtomography
000285487 650_2 $$2MeSH$$aBone Density
000285487 650_2 $$2MeSH$$aMale
000285487 650_2 $$2MeSH$$aHumans
000285487 650_2 $$2MeSH$$aCell Differentiation
000285487 650_2 $$2MeSH$$aSuperoxide Dismutase
000285487 7001_ $$aRamge, Jan-Moritz$$b1
000285487 7001_ $$0P:(DE-2719)2812844$$aWiesner, Diana$$b2$$udzne
000285487 7001_ $$0P:(DE-2719)9001282$$aScekic-Zahirovic, Jelena$$b3$$udzne
000285487 7001_ $$aAntonucci, Stefano$$b4
000285487 7001_ $$aNungeß, Sandra$$b5
000285487 7001_ $$aGebauer, Dorothea$$b6
000285487 7001_ $$aIgnatius, Anita$$b7
000285487 7001_ $$0P:(DE-2719)9000455$$aWeishaupt, Jochen H$$b8
000285487 7001_ $$aHaffner-Luntzer, Melanie$$b9
000285487 7001_ $$0P:(DE-2719)2812851$$aRoselli, Francesco$$b10$$eLast author$$udzne
000285487 773__ $$0PERI:(DE-600)2874757-4$$a10.1172/jci.insight.197475$$gVol. 11, no. 5, p. e197475$$n5$$pe197475$$tJCI insight$$v11$$x2379-3708$$y2026
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