五、总结
骨硬化小鼠模型为科学家们解读破骨细胞分化和骨吸收功能的生物学基础提供了有力的手段。比如，op/op小鼠的骨硬化症表现引导了M-CSF在破骨细胞分化中必要功能的发现；atp6i-/-和oc/oc小鼠的研究和报道为第一例人类ATP6i突变相关的骨硬化症报道提供了指导；破骨细胞分化相关的RANKL-RANKTRAF6信号通路轴及ITAM辅助信号通路的阐释离不开通路上信号蛋白相关的敲除小鼠模型的建立 (RANKL-/-、RANK-/-、TRAF6-/-、 FcRγ-/- DAPl2-/-、 FcRγ-/- DAPl2-/-、 Btk-/-Tec-/-等)；巨噬细胞-破骨细胞系的谱系决定和分化的研究也依赖于转录因子相关的基因缺陷小鼠的发现和建立 (c-fos-/-、PU.l-/-等)；而 β-整合素蛋白缺陷小鼠、c-Src-/-小鼠、cdc42-/-小鼠和racl/rac2条件性敲除小鼠模型的建立引导研究者们勾画出了调节破骨精细细胞骨架结构的信号通路。
骨硬化病作为一种罕见病，却由于多样的致病基因导致不同的发病表现，也因致病基因的不同需要不同的治疗手段。目前骨硬化症主要的有效治疗手段是骨髓移植，然而并非所有的骨硬化症都可以通过骨髓移植治愈，如骨硬化症并发的神经性疾病无法通过骨髓移植治愈，同时移植后的免疫排斥也成为术后高死亡率的主要顾虑。骨硬化症小鼠模型为探索其他的治疗手段提供了很好的平台。建立更接近于人类疾病的骨硬化症小鼠模型，并针对这些小鼠模型开发包括基因治疗在内的更有效治疗手段，将成为今后研究的主要方向之一。
（吴梦瑞 李亦平）
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