Musculoskeletal regeneration最新文献

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Distribution of myosin heavy chain isoforms in muscular dystrophy: insights into disease pathology 肌萎缩症中肌球蛋白重链异构体的分布:对疾病病理学的见解
Musculoskeletal regeneration Pub Date : 2016-07-05 DOI: 10.14800/MR.1365
Aaron M. Beedle
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引用次数: 7
Distribution of myosin heavy chain isoforms in muscular dystrophy: insights into disease pathology. 肌萎缩症中肌球蛋白重链异构体的分布:对疾病病理学的见解。
Musculoskeletal regeneration Pub Date : 2016-01-01 Epub Date: 2016-07-05
Aaron M Beedle
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引用次数: 0
A mouse model of craniofacial bone lesion of tuberous sclerosis complex. 结节性硬化症颅面骨损伤小鼠模型。
Musculoskeletal regeneration Pub Date : 2015-01-01 DOI: 10.14800/mr.814
Fang Fang, Xiaoxi Wei, Min Hu, Fei Liu
{"title":"A mouse model of craniofacial bone lesion of tuberous sclerosis complex.","authors":"Fang Fang,&nbsp;Xiaoxi Wei,&nbsp;Min Hu,&nbsp;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}
引用次数: 6
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