SLIT3 promotes myogenic differentiation as a novel therapeutic factor against muscle loss

Autor: Han Jin Cho, Hyeonmok Kim, Young‐Sun Lee, Sung Ah Moon, Jin‐Man Kim, Hanjun Kim, Min Ji Kim, Jiyoung Yu, Kyunggon Kim, In‐Jeoung Baek, Seung Hun Lee, Kyong Hoon Ahn, Sungsub Kim, Jong‐Sun Kang, Jung‐Min Koh
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 12, Iss 6, Pp 1724-1740 (2021)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12769
Popis: Abstract Background Sarcopenia and osteoporosis frequently co‐occur in the elderly and have common pathophysiological determinants. Slit guidance ligand 3 (SLIT3) has been recently discovered as a novel therapeutic factor against osteoporosis, and a SLIT3 fragment containing the second leucine‐rich repeat domain (LRRD2) had a therapeutic efficacy against osteoporosis. However, a role of SLIT3 in the skeletal muscle is unknown. Methods Skeletal muscle mass, strength, and/or physical activity were evaluated in Slit3−/−, ovariectomized, and aged mice, based on the measurements of muscle weight and grip strength, Kondziella's inverted hanging test, and/or wheel‐running test. Skeletal muscles were also histologically evaluated by haematoxylin and eosin staining and/or immunofluorescence. The ovariectomized and aged mice were intravenously injected with recombinant SLIT3 LRRD2 for 4 weeks. C2C12 cells were used to know cellular effects of SLIT3, such as in vitro myogenesis, fusion, cell viability, and proliferation, and also used to evaluate its molecular mechanisms by immunocytochemistry, immunoprecipitation, western blotting, real‐time PCR, siRNA transfection, and receptor‐ligand binding ELISA. Results Slit3‐deficient mice exhibited decreased skeletal muscle mass, muscle strength, and physical activity. The relative masses of gastrocnemius and soleus were lower in the Slit3−/− mice (0.580 ± 0.039% and 0.033 ± 0.003%, respectively) than those in the WT littermates (0.622 ± 0.043% and 0.038 ± 0.003%, respectively) (all, P
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