Abstract：
Osteofibrous dysplasia (OFD) is a rare, benign, fibro-osseous lesion that occurs most commonly in the tibia of children. Tibial involvement leads to bowing and predisposes to the development of a fracture which exhibit significantly delayed healing processes, leading to prolonged morbidity. We previously identified gain-of-function mutations in the MET gene as a cause for OFD. In our present study, we test the hypothesis that gain-of-function MET mutations impair bone repair due to reduced osteoblast differentiation. A heterozygous Met exon 15 skipping (MetΔ15-HET) mouse was created to imitate the human OFD mutation. The mutation results in aberrant and dysregulation of MET-related signaling determined by RNA-seq in the murine osteoblasts extracted from the wide-type and genetic mice. Although no gross skeletal defects were identified in the mice, fracture repair was delayed in MetΔ15-HET mice, with decreased bone formation observed 2-week postfracture. Our data are consistent with a novel role for MET-mediated signaling regulating osteogenesis.
摘要：
骨纤维发育不良（OFD）是一种罕见的，良性,最常见于儿童胫骨的纤维骨损伤。胫骨受累导致弯曲并易于发生骨折，骨折的愈合过程显着延迟。导致长期发病。我们先前确定MET基因中的功能获得性突变是OFD的原因。在我们目前的研究中，我们检验了功能获得MET突变由于成骨细胞分化减少而损害骨修复的假设.产生杂合Met外显子15跳跃(MetA15-HET)小鼠以模仿人OFD突变。该突变导致从宽型和遗传小鼠中提取的鼠成骨细胞中由RNA-seq确定的MET相关信号的异常和失调。尽管在小鼠中没有发现明显的骨骼缺陷，MetΔ15-HET小鼠骨折修复延迟，骨折后2周观察到骨形成减少。我们的数据与MET介导的信号调节成骨的新作用一致。
