PDF(Pubmed)
Abstract：
UNASSIGNED: The dysregulation of cell fate toward osteoprecursor cells associated with most GNAS-based disorders may lead to episodic de novo extraskeletal or ectopic bone formation in subcutaneous tissues. The bony lesion distribution suggests the involvement of abnormal differentiation of mesenchymal stem cells (MSCs) and/or more committed precursor cells. Data from transgenic mice support the concept that GNAS is a crucial factor in regulating lineage switching between osteoblasts (OBs) and adipocyte fates. The mosaic nature of heterotopic bone lesions suggests that GNAS genetic defects provide a sensitized background for ectopic osteodifferentiation, but the underlying molecular mechanism remains largely unknown.
UNASSIGNED: The effect of GNAS silencing in the presence and/or absence of osteoblastic stimuli was evaluated in the human L88/5 MSC line during osteodifferentiation. A comparison of the data obtained with data coming from a bony lesion from a GNAS-mutated patient was also provided.
UNASSIGNED: Our study adds some dowels to the current fragmented notions about the role of GNAS during osteoblastic differentiation, such as the premature transition of immature OBs into osteocytes and the characterization of the differences in the deposed bone matrix.
UNASSIGNED: We demonstrated that our cell model partially replicates the in vivo behavior results, resulting in an applicable human model to elucidate the pathophysiology of ectopic bone formation in GNAS-based disorders.
UNASSIGNED: The effect of GNAS silencing in the presence and/or absence of osteoblastic stimuli was evaluated in the human L88/5 MSC line during osteodifferentiation. A comparison of the data obtained with data coming from a bony lesion from a GNAS-mutated patient was also provided.
UNASSIGNED: Our study adds some dowels to the current fragmented notions about the role of GNAS during osteoblastic differentiation, such as the premature transition of immature OBs into osteocytes and the characterization of the differences in the deposed bone matrix.
UNASSIGNED: We demonstrated that our cell model partially replicates the in vivo behavior results, resulting in an applicable human model to elucidate the pathophysiology of ectopic bone formation in GNAS-based disorders.
摘要：
■与大多数基于GNAS的疾病相关的骨前体细胞的细胞命运失调可能导致皮下组织中偶发的从头骨或异位骨形成。骨病变分布提示间充质干细胞（MSC）和/或更多定型前体细胞的异常分化。来自转基因小鼠的数据支持以下概念：GNAS是调节成骨细胞（OB）和脂肪细胞命运之间谱系转换的关键因素。异位骨病变的镶嵌性质表明，GNAS遗传缺陷为异位骨分化提供了敏感的背景，但是潜在的分子机制在很大程度上仍然未知。
■在骨分化期间在人L88/5MSC系中评估在存在和/或不存在成骨细胞刺激的情况下GNAS沉默的效果。还提供了获得的数据与来自GNAS突变患者的骨损伤的数据的比较。
■我们的研究为当前关于GNAS在成骨细胞分化过程中的作用的零碎观念增加了一些销钉，例如未成熟OB过早转变为骨细胞以及沉积骨基质的差异表征。
■我们证明了我们的细胞模型部分复制了体内行为结果，产生了一个适用的人类模型，以阐明基于GNAS的疾病中异位骨形成的病理生理学。
■在骨分化期间在人L88/5MSC系中评估在存在和/或不存在成骨细胞刺激的情况下GNAS沉默的效果。还提供了获得的数据与来自GNAS突变患者的骨损伤的数据的比较。
■我们的研究为当前关于GNAS在成骨细胞分化过程中的作用的零碎观念增加了一些销钉，例如未成熟OB过早转变为骨细胞以及沉积骨基质的差异表征。
■我们证明了我们的细胞模型部分复制了体内行为结果，产生了一个适用的人类模型，以阐明基于GNAS的疾病中异位骨形成的病理生理学。
