神经递质P物质含量减少可抑制成骨细胞分化并导致骨质疏松

Reduction of substance P enhances osteoporotic effects by depress the differentiation of osteoblasts

目的研究神经递质P物质调控成骨细胞分化的分子途径，探讨神经损伤后导致废用性骨质疏松的发病机制。方法分离骨髓基质干细胞进行原代及传代培养；绘制细胞生长曲线并对培养细胞进行诱导，使其向成骨细胞分化，行碱性磷酸酶染色鉴定成骨细胞，分别采用P物质及其受体拮抗剂进行干预；抽提细胞总RNA，用RT—PCR检测Osterix基因的表达。结果骨髓基质干细胞在生长对数增殖期为4—6d，经碱性磷酸酶染色证实为成骨细胞。采用RT—PCR检测发现P物质受体拮抗剂干预成骨细胞分化，导致成骨细胞分化过程中重要的转录引子Osterix基因表达下调，从而抑制前成骨细胞向成骨细胞转化，进而导致骨重建的负向平衡，最终导致骨质疏松。结论P物质含量减少可导致前成骨细胞中转录因子Ostrix及Runx2基因表达下调，抑制其向成骨细胞分化。这可能是神经损伤后导致废用性骨质疏松的发病机制。

Objective To research on the molecular pathway of substance P-induced osteoblast differentiation and discuss the mechanism of osteoporosis after nerve injury. Methods Mesenchymal stem cells were isolated and cultured ; the cell growth curve was drawn. Substance P receptor（ NK1 ） antagonist or Substance P was used to interfere with osteoblast differentiation respectively ; total RNA was extracted and Ostrix gene expression was evaluated by RT-PCR. Results Mesenchymal stem cells logarithmic proliferation time was 4 - 6 d, the osteoblast was confirmed by positive alkaline phosphatase （ALP） dyeing. Substance P receptor（ NK1 ） antagonist interfere with osteoblast differentiation though downregulate the important transcription fator Ostrix gene expression, which depress mesenchymal stem cells differentiate to osteoblast and leading to osteoporosis ultimately. Conclusion Reduction of substance P may downregulate Ostrix gene expression; depress mesenchymal stem cells differentiate to osteoblast. It is one important pathway of disuse osteoporosis after trauma of nerve.