Regulatory mechanisms of bone metabolism by nervous system

我们建立了p38α突变小鼠（sem小鼠），其p38α底物对接位点编码区存在点突变，可作为p38α功能缺失的有限模型。在本研究中，我们利用sem小鼠和野生型同窝小鼠（wt小鼠）研究p38α在骨代谢和神经再生中的生理作用。在骨代谢方面，sem小鼠骨密度明显高于野生型小鼠，这可能与其抑制了破骨细胞的分化有关。在神经再生方面，我们证实了挤压伤后sem小鼠的组织学和功能性神经恢复比野生型小鼠延迟。为了研究这些发现的潜在机制，我们检测了坐骨神经的炎症反应，发现挤压损伤后TNF-α、IL-1β、Caspase-3和Tenascin-C表现出不同的表达模式。这是第一项证明p38α在骨代谢和神经再生中的生理作用而不使用药理学抑制剂的研究。

We generated novel p38αmutant mice (sem mice) with a point mutation in the region encoding the p38αsubstrate-docking-site, which serves as a limited loss-of-function model of p38α. In the present study, we utilized sem mice and wild-type littermates (wt mice) to investigate the physiological role of p38αin bone metabolism and in nerve regeneration. In bone metabolism, sem mice showed higher bone density compared with wt mice, which could come from the inhibition of the osteoclast differentiation. In nerve regeneration, we confirmed that histological and functional nerve recovery following crush injury was delayed in sem mice compared with that in wt mice. To investigate the underlying mechanisms of these findings, we examined inflammatory responses of the sciatic nerve, and found that TNF-α, IL-1β, Caspase-3 and Tenascin-C showed different expression patterns following crush injury. This is the first study demonstrating physiological role of p38αin bone metabolism and in nerve regeneration without the use of pharmacological inhibitors.