Home > In process > Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model. > print

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024 7 _ |a 10.1172/jci.insight.197475
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037 _ _ |a DZNE-2026-00263
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Özkan, Burak
|b 0
245 _ _ |a Reduced osteogenic factors and early osteoblast senescence in SOD1(G93A) ALS mouse model.
260 _ _ |a Ann Arbor, Michigan
|c 2026
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520 _ _ |a Amyotrophic 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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650 _ 7 |a Bone biology
|2 Other
650 _ 7 |a Cell biology
|2 Other
650 _ 7 |a Cellular senescence
|2 Other
650 _ 7 |a Neurodegeneration
|2 Other
650 _ 7 |a Neuroscience
|2 Other
650 _ 7 |a Osteoclast/osteoblast biology
|2 Other
650 _ 7 |a Superoxide Dismutase-1
|0 EC 1.15.1.1
|2 NLM Chemicals
650 _ 7 |a SOD1 G93A protein
|0 EC 1.15.1.1
|2 NLM Chemicals
650 _ 7 |a Sod1 protein, mouse
|0 EC 1.15.1.1
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650 _ 7 |a Superoxide Dismutase
|0 EC 1.15.1.1
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: genetics
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: pathology
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: physiopathology
|2 MeSH
650 _ 2 |a Osteoblasts: metabolism
|2 MeSH
650 _ 2 |a Osteoblasts: pathology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Superoxide Dismutase-1: genetics
|2 MeSH
650 _ 2 |a Superoxide Dismutase-1: metabolism
|2 MeSH
650 _ 2 |a Osteogenesis: genetics
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Cellular Senescence: genetics
|2 MeSH
650 _ 2 |a X-Ray Microtomography
|2 MeSH
650 _ 2 |a Bone Density
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Cell Differentiation
|2 MeSH
650 _ 2 |a Superoxide Dismutase
|2 MeSH
700 1 _ |a Ramge, Jan-Moritz
|b 1
700 1 _ |a Wiesner, Diana
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700 1 _ |a Scekic-Zahirovic, Jelena
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700 1 _ |a Antonucci, Stefano
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700 1 _ |a Nungeß, Sandra
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700 1 _ |a Gebauer, Dorothea
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700 1 _ |a Ignatius, Anita
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700 1 _ |a Weishaupt, Jochen H
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700 1 _ |a Haffner-Luntzer, Melanie
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700 1 _ |a Roselli, Francesco
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773 _ _ |a 10.1172/jci.insight.197475
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