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• W3031078403 endingPage "e3000731" @default.
• W3031078403 startingPage "e3000731" @default.
• W3031078403 abstract "The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging–like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C–deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C–deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C–KO mice diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-β-gal), p16Ink4a, and p53 in lamin A/C–deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis." @default.
• W3031078403 created "2020-06-05" @default.
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• W3031078403 date "2020-06-01" @default.
• W3031078403 modified "2023-10-16" @default.
• W3031078403 title "Linking skeletal muscle aging with osteoporosis by lamin A/C deficiency" @default.
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• W3031078403 doi "https://doi.org/10.1371/journal.pbio.3000731" @default.
• W3031078403 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7310860" @default.
• W3031078403 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32479501" @default.
• W3031078403 hasPublicationYear "2020" @default.
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