血浆纤连蛋白在成骨细胞增殖及II型糖尿病种植体骨整合中的作用和机制研究

Plasma fibronectin (pFN) is a major component of noncollagenous bone matrix which controls the biomechanical property of bone. Our previous studies also showed that pFN deficiency would affect osteoblast extracellular matrix assembly and inhibit its mineralization, but its effect and underlying mechanism on osteoblast proliferation is unclear. Studies revealed that insulin promoted osteoblast proliferation and differentiation via its receptor through activation of PI3K/Akt and MAPK/ERK signaling pathways. Furthermore, the insulin receptor (IR) molecule contains three FN type III modules which are important for FN matrix assembly. Thus, we speculate that pFN may bind to IR molecule and promote osteoblast proliferation through activation of the same signaling pathways. On the other hand, patients with type II diabetes mellitus suffer from decreased osseointegration in dental implant because of insulin deficiency, we apply pFN locally and establish the complex of pFN, bone marrow stroma cell and titanium implant, which will guarantee dental implant osseointegration in type II diabetes mellitus. This study will not only help to elucidate the role and mechanism of pFN in osteoblast proliferation, but also provide theoretical basis for the application of pFN in the compensation of the shortage of insulin and guarantee of implant osseointegration in type II diabetes mellitus.

血浆纤连蛋白（plasma fibronectin, pFN）为非胶原性骨基质的重要组成成分并调控骨的生物机械性能。申请人前期研究也表明pFN缺乏会影响成骨细胞细胞外基质沉积并抑制其矿化，但其在成骨细胞增殖中的作用机制尚不清楚。研究表明胰岛素通过其受体介导激活PI3K/Akt和MAPK/ERK信号通路，促进成骨细胞增殖和分化，而胰岛素受体分子中含有三个FN III型模块，该模块对FN 基质沉积非常重要。因此我们推测pFN可能与胰岛素受体结合，通过激活下游信号通路介导成骨细胞增殖。此外II糖尿病患者由于胰岛素相对缺乏导致牙种植术中种植体骨整合效果不佳，本课题中通过局部应用pFN, 构建pFN+骨髓基质细胞+种植体复合体，以期保障II型糖尿病种植体骨整合效果。本研究不仅有助于阐明pFN在成骨细胞增殖中的作用机制，还为局部应用pFN弥补胰岛素不足保障II型糖尿病种植体疗效提供理论基础。