Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva
Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva
复制标题
DOI：
10.1056/nejm199608223350804
复制
发表时间：
1996-08-22
影响因子：
158.5
通讯作者：
Kaplan, FS
中科院分区：
文献类型：
--
作者：
Shafritz, AB;Shore, EM;Kaplan, FS
研究背景进行性纤维发育不良是一种遗传性结缔组织疾病，主要表现为先天性拇趾畸形和后天异位骨形成，虽然早在300多年前就已被描述，但其遗传缺陷和病理生理机制仍不清楚。骨形态发生蛋白是一种强有力的骨诱导因子，参与骨骼的发育组织，其中一种或多种蛋白质的产生增加被认为是进行性骨化性纤维发育不良的原因。方法我们研究了进展性纤维发育不良患者外周血单个核细胞建立的淋巴母细胞系以及来源于皮损和非皮损组织的成纤维细胞样细胞系。结果在检测到的骨形态发生蛋白中，只有骨形态发生蛋白4及其mRNA在进行性纤维发育不良早期纤维增生性病变的细胞中表达升高，而在32例进行性纤维发育不良患者的淋巴母细胞系中仅1例有骨形态发生蛋白4mRNA的表达(P<0.05)。
Background Fibrodysplasia ossificans progressiva is a heritable disorder of connective tissue characterized by congenital malformation of the great toes and postnatal formation of ectopic bone, Although the disorder was first described more than 300 years ago, the genetic defect and pathophysiology remain unknown. Bone morphogenetic proteins are potent bone-inducing morphogens that participate in the developmental organization of the skeleton, and increased production of one or more of these proteins has been proposed as the cause of fibrodysplasia ossificans progressiva.Methods We studied lymphoblastoid cell lines established from peripheral-blood mononuclear cells of patients with fibrodysplasia ossificans progressiva and fibroblast-like cell lines derived from lesional and nonlesional tissue. We used Northern blot analysis and ribonuclease protection assays to measure the expression of messenger RNA (mRNA) of bone morphogenetic proteins 1 to 7 and immunohistochemical analysis to examine protein expression.Results Among the bone morphogenetic proteins and mRNAs examined, only bone morphogenetic protein 4 and its mRNA were present in increased levels in cells derived from an early fibroproliferative lesion in a patient with fibrodysplasia ossificans progressiva, Bone morphogenetic protein 4 mRNA was expressed in lymphoblastoid cell lines from 26 of 32 patients with fibrodysplasia ossificans progressiva but from only 1 of 12 normal subjects (P