{"title":"Distribution of myosin heavy chain isoforms in muscular dystrophy: insights into disease pathology","authors":"Aaron M. Beedle","doi":"10.14800/MR.1365","DOIUrl":"https://doi.org/10.14800/MR.1365","url":null,"abstract":"Myosin heavy chain isoforms are an important component defining fiber type specific properties in skeletal muscle, such as oxidative versus glycolytic metabolism, rate of contraction, and fatigability. While the molecular mechanisms that underlie specification of the different fiber types are becoming clearer, how this programming becomes disrupted in muscular dystrophy and the functional consequences of fiber type changes in disease are not fully resolved. Fiber type changes in disease, with specific focus on muscular dystrophies caused by defects in the dystrophin glycoprotein complex, are discussed.","PeriodicalId":90929,"journal":{"name":"Musculoskeletal regeneration","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66656735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Distribution of myosin heavy chain isoforms in muscular dystrophy: insights into disease pathology.","authors":"Aaron M Beedle","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Myosin heavy chain isoforms are an important component defining fiber type specific properties in skeletal muscle, such as oxidative versus glycolytic metabolism, rate of contraction, and fatigability. While the molecular mechanisms that underlie specification of the different fiber types are becoming clearer, how this programming becomes disrupted in muscular dystrophy and the functional consequences of fiber type changes in disease are not fully resolved. Fiber type changes in disease, with specific focus on muscular dystrophies caused by defects in the dystrophin glycoprotein complex, are discussed.</p>","PeriodicalId":90929,"journal":{"name":"Musculoskeletal regeneration","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34581654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A mouse model of craniofacial bone lesion of tuberous sclerosis complex.","authors":"Fang Fang, Xiaoxi Wei, Min Hu, Fei Liu","doi":"10.14800/mr.814","DOIUrl":"https://doi.org/10.14800/mr.814","url":null,"abstract":"<p><p>The mammalian/mechanistic target of rapamycin (mTOR) signaling pathway plays critical roles in skeletal development. The impact and underlying mechanisms of its dysregulation in bone homeostasis is poorly defined. The best known and characterized mTOR signaling dysregulation in human disease is called Tuberous Sclerosis Complex (TSC). TSC is an autosomal dominant neurocutaneous syndrome with a high frequency (>66%) of osseous manifestations such as sclerotic lesions in the craniofacial region. TSC is caused by mutations of TSC1 or TSC2, the heterodimer protein inhibitor of mTORC1 signaling. The underlying mechanism of bone lesions in TSC is unclear. We generated a TSC mouse model with TSC1 deletion in neural crest derived (NCD) cells, which recapitulated the sclerotic craniofacial bone lesion in TSC patients. We demonstrated that TSC1 null NCD osteoblasts overpopulated the NCD bones and the resultant increased bone formation is responsible for the sclerotic bone phenotype. Mechanistically, osteoblast number increase is due to the hyperproliferation of osteoprogenitor cells at an early postnatal stage. Noteworthy, administration of rapamycin, an mTORC1 inhibitor at early postnatal stage can completely rescue the excess bone acquisition, but late treatment cannot. Altogether, our data suggested that enhanced mTORC1 signaling in NCD cells can enlarge the osteoprogenitor pool and lead to the excess bone acquisition, which is likely the underlying mechanism of sclerotic bone lesion observed in TSC patients.</p>","PeriodicalId":90929,"journal":{"name":"Musculoskeletal regeneration","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456023/pdf/nihms690479.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33249417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}