Shriners Hospital for Children-Canada, Montreal, Quebec, Canada.
J Bone Miner Res. 2019 Feb;34(2):207-214. doi: 10.1002/jbmr.3617. Epub 2018 Nov 29.
Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I encoding genes. Recent studies in mouse models of recessive OI, Crtap mice, and dominant OI, +/G610C mice, found that application of a transforming growth factor beta (TGF-β) neutralizing antibody 1D11 rescues the bone phenotype. In the present study, we investigated TGF-β signaling in a mouse model of severe dominant OI with a high incidence of spontaneous fractures, Col1a1 mice, and the effect of TGF-β neutralizing antibody 1D11 on bone phenotype in 8-week-old mice. Col1a1 mice had elevated TGF-β signaling in bone tissue. Treatment of Col1a1 mice with 1D11 was associated with increased bone length but had no significant effect on bone mass or bone mechanical properties, and no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity) or resorption (tartrate-resistant acid phosphatase) were found. Our data thus indicate that the TGF-β neutralizing antibody 1D11 is not effective in a mouse model of dominant OI with a high incidence of spontaneous fractures. © 2018 American Society for Bone and Mineral Research.
成骨不全症（OI）是一种遗传性骨脆弱疾病，通常由影响 I 型胶原编码基因的突变引起。最近在隐性 OI 的小鼠模型（Crtap 小鼠）和显性 OI 的小鼠模型（+/G610C 小鼠）中的研究发现，应用转化生长因子β（TGF-β）中和抗体 1D11 可挽救骨表型。在本研究中，我们研究了 TGF-β信号通路在一种具有高自发性骨折发生率的严重显性 OI 小鼠模型（Col1a1 小鼠）中的作用，以及 TGF-β中和抗体 1D11 对 8 周龄小鼠骨表型的影响。Col1a1 小鼠的骨组织中 TGF-β信号通路被激活。用 1D11 处理 Col1a1 小鼠可增加骨长度，但对骨量或骨力学性能没有显著影响，且血清骨形成标志物（碱性磷酸酶活性）或骨吸收标志物（抗酒石酸酸性磷酸酶）也没有发现有治疗相关的差异。因此，我们的数据表明，TGF-β中和抗体 1D11 在自发性骨折发生率较高的显性 OI 小鼠模型中无效。©2018 美国骨骼与矿物质研究协会。
