脂肪因子vaspin调控骨形成的作用及其分子机制

Our previous study demonstrated that vaspin, a novel adipocytokine, protects osteoblasts from apoptosis by activating MAPK/ERK signal pathway and promotes osteoblastic differentiation. However, the role of vaspin in regulating osteogenesis and its mechanism is still unclear. This study is to investigate the effect of vaspin in regulating osteogenesis and its potential molecular mechanism. To detect the expression of vaspin receptor GRP78 on celluar surface of osteogenic precursor cells, immunofluorescence staining will be used. To observe the influence of vaspin on osteoblastic differentiation, ALP activity, the expression of OC, Runx2 and OPN, formation of mineral nodes will be measured. To evaluate the role of vaspin on cellular signaling passway in osteoblastic differentiation, Western blotting will be used. To demonstrate that vaspin mediates osteoblastic differentiation by binding with its receptor GRP78, GRP78 siRNA will be used. To investigate the effects of vaspin in ovariectomized mice, serum levels of ALP, osteoblastic biomarkers, bone mineral density and bone microarchitecture will be detected. Our research aims to further identify the potential mechanisms of vaspin on regulating osteogenesis to provide a new theoretical basis and novel drugs for the prevention and treatment of osteoporosis.

我们前期的研究证实：新近发现的脂肪因子Vaspin通过激活MAPK/ERK信号通路，抑制成骨细胞凋亡，并可促进成骨细胞分化。但vaspin调控骨形成的作用及机制尚不明确。本课题探讨Vaspin调控骨形成的作用及其分子机制，采用免疫荧光细胞化学法检测Vaspin受体GRP78在成骨前体细胞表面的表达情况,观察Vaspin对成骨细胞分化过程中GRP78表达的影响；研究Vaspin对成骨分化过程中ALP活性、成骨标志物表达以及矿化结节形成的影响，Western blot检测其对信号转导通路的影响；构建GRP78 siRNA敲除GRP78基因，观察其对成骨细胞分化的影响，证实Vaspin通过与其受体GRP78结合发挥调控作用；研究Vaspin干预对去卵巢大鼠血清ALP、成骨标志物、骨密度和骨微结构的影响。本研究深入探索Vaspin调控骨形成的机制，试图为骨质疏松症的防治提供新的理论基础和治疗药物。

我们前期的研究证实：新近发现的脂肪因子Vaspin通过激活MAPK/ERK信号通路，抑制成骨细胞凋亡，并可促进成骨细胞分化。但vaspin调控骨形成的作用及机制尚不明确。本课题探讨Vaspin调控骨形成的作用及其分子机制，采用免疫荧光细胞化学法检测Vaspin受体GRP78在成骨前体细胞表面的表达情况,观察Vaspin对成骨细胞分化过程中GRP78表达的影响；研究Vaspin对成骨分化过程中ALP活性、成骨标志物表达以及矿化结节形成的影响，Western blot检测其对信号转导通路的影响；构建GRP78 siRNA敲除GRP78基因，观察其对成骨细胞分化的影响，证实Vaspin通过与其受体GRP78结合发挥调控作用；研究Vaspin干预对去卵巢大鼠血清ALP、成骨标志物、骨密度和骨微结构的影响。本研究深入探索Vaspin调控骨形成的机制，试图为骨质疏松症的防治提供新的理论基础和治疗药物。