Julius Wolff Institute and Center for Musculoskeletal Surgery, Charite Universitätsmedizin Berlin, Germany.
Bone. 2012 Oct;51(4):651-60. doi: 10.1016/j.bone.2012.07.011. Epub 2012 Jul 31.
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease resulting from inactivating mutations in the gene encoding the protein neurofibromin. NF1 manifests as a heritable susceptibility to tumours of neural tissue mainly located in the skin (neurofibromas) and pigmented skin lesions. Besides these more common clinical manifestations, many NF1 patients (50%) have abnormalities of the skeleton. Long bones are often affected (usually the tibia) and the clinical signs range from bowing to spontaneous fractures and non-unions. Here we present the analysis of bone fracture healing in the Nf1(Prx1)-knock-out mouse, a model of NF1 long bone dysplasia. In line with previously reported cortical bone injury results, fracture healing was impaired in Nf1(Prx1) mice. We showed that the defective fracture healing in Nf1(Prx1) mice is characterized by diminished cartilaginous callus formation and a thickening of the periosteal bone. These changes are paralleled by fibrous tissue accumulation within the fracture site. We identify a population of fibrous tissue cells within the Nf1 deficient fracture as alpha-smooth muscle actin positive myofibroblasts. Additionally, histological and in-situ hybridization analysis reveal a direct contact of the fracture site with muscle fascia, suggesting a possible involvement of muscle derived cells in the fracture deterioration.
神经纤维瘤病 1 型（NF1）是一种常染色体显性遗传疾病，由编码神经纤维瘤蛋白的基因突变导致失活。NF1 表现为对主要位于皮肤（神经纤维瘤）和色素性皮肤病变的神经组织肿瘤的遗传性易感性。除了这些更常见的临床表现外，许多 NF1 患者（50%）骨骼异常。长骨经常受到影响（通常是胫骨），临床症状从弯曲到自发性骨折和不愈合。在这里，我们分析了 Nf1(Prx1)-敲除小鼠的骨骨折愈合，这是 NF1 长骨发育不良的模型。与先前报道的皮质骨损伤结果一致，Nf1(Prx1) 小鼠的骨折愈合受损。我们表明，Nf1(Prx1) 小鼠的骨折愈合缺陷的特征是软骨性骨痂形成减少和骨膜骨增厚。这些变化与骨折部位内纤维组织的积累平行。我们在 Nf1 缺陷骨折中发现了一群纤维组织细胞为α-平滑肌肌动蛋白阳性成肌纤维细胞。此外，组织学和原位杂交分析显示骨折部位与肌肉筋膜直接接触，表明肌肉来源细胞可能参与骨折恶化。
