神经肽Y促进植骨融合骨再生早期破骨细胞增殖的作用机制研究

Spinal fusion commonly used in surgical treatment of spinal diseases. Bone regeneration is the essential process for graft fusion. Fusion failure is one of the worst complications accompanying spinal fusion technique, which is due to abnormal regulation of the early stage of bone regeneration. Osteoclast plays key role during early stage of bone regeneration, recruiting osteoblasts and promoting angiogenesis. How osteoclasts are regulated is unknown. Neuropeptide Y (NPY) is an endocrine neuropeptide, which is early distributed in active bone regeneration area where osteoclasts and osteoblasts exist. Yet, little is known about the function of increased NPY during early stage of bone regeneration. Therefore, the purpose of this study is to elucidate whether NPY accelerates bone regeneration in spinal fusion via activating osteoclasts during the early stage. In rat spinal fusion model, we will employ micro-CT analysis and in vivo imaging technology to determine: 1) role of NPY during the early stage of bone regeneration in spinal fusion; 2) role of osteoclasts in mediating effects of NPY on bone regeneration; 3) effect of RANKL-RANK signaling on the role of NPY activation of osteoclasts. This project will confirm NPY promotes bone regeneration in spinal fusion by activating osteoclasts during the early stage, and would provide new strategies to accelerate spinal fusion.

脊柱融合术是脊柱外科最常用的手术方式。植骨融合骨再生是脊柱融合的关键过程，早期再生障碍可以导致融合手术失败。破骨细胞是骨再生早期关键调控因素，可以促进血管新生和成骨细胞招募，然而早期破骨细胞活化的机制不明。神经肽Y（neuropeptide Y，NPY）是一种神经内分泌因子，早期广泛分布于植骨融合骨再生活跃区域，但是作用和机制不明确。因此，本课题总体目标是明确NPY激活破骨细胞促进早期植骨融合骨再生的作用和机制。 通过建立脊柱融合动物模型，运用micro-CT和动物在体实时观察等技术，拟明确：1）NPY在早期植骨融合骨再生的作用和意义；2）破骨细胞介导NPY促进早期骨再生的作用机制；3）NPY通过激活RANKL-RANK通路促进破骨细胞增殖和活化。通过本研究将揭示植骨融合骨再生早期破骨细胞活化的机制，明确NPY对骨再生早期的调控作用和意义，为加快脊柱融合骨再生提供新的治疗手段和研究方向。