维生素C对骨骼发育、骨密度的影响及其分子作用机制

Bone health is closely associated with the nutritional status of the organism. Many studies show that vitamin C can stimulate the synthesis of procollagen and collagen, activate alkaline phosphatase, and promote the formation of osteoblasts, suggesting that vitamin C also plays an important role in maintaining bone health. However, the exact role of vitamin C on the health of the human skeleton is still controversial; its role in bone development is basically unknown. There is evidence that vitamin C may play a role in bone development and bone density regulation through affecting the proliferation and differentiation of mesenchymal stem cells, osteoblasts, and osteoclasts. Thus far vitamin C may play a greater role in the prevention and management of osteoporosis. In order to clarify the best dose and exact molecular mechanisms by which vitamin C regulates bone development and bone mineral density, the proposed study will perform a dynamic gene expression microarray assay on the murine natural mutation model of vitamin C deficiency - SFX, which was identified by our lab recently. The impact of vitamin C on transcriptomic changes and regulatory networks associated with early femoral development (1-28 days) will be identified and their potential gender variations will be analyzed. The optimal dose for vitamin C replacement therapy will be established, which will provide scientific evidence for rational clinical use of vitamin C in the prevention and treatment of osteoporosis.

机体营养与骨骼健康密切相关，研究发现维生素C可刺激前胶原、促进胶原蛋白合成；刺激碱性磷酸酶、促进造骨细胞形成，提示维生素C在维护骨骼健康中起着重要作用。但目前有关维生素C对人体骨骼发育过程中的确切作用机制尚不明确。研究表明，维生素C可通过影响间充质干细胞、成骨细胞和破骨细胞的增殖分化而在骨骼发育和骨密度调节中发挥重要作用。因此，维生素C在当前骨质疏松症的综合防治中可能发挥更大作用。为了弄清维生素C调节骨骼发育的最佳剂量及其影响骨密度的确切分子作用机制，本项目利用首次建立的自然突变维生素C缺陷模型-SFX小鼠、采用基因表达芯片技术从系统生物学角度动态分析维生素C对小鼠早期骨骼发育（1-28天）中基因表达谱的影响、找到维生素C在小鼠早期骨骼发育中的调控网络及可能存在的性别差异，确定维生素C的替代治疗的最佳剂量，为临床合理使用维生素C防治骨质疏松症提供科学依据。

项目主持人多年从事分子生物学研究，在美国UTHSC的实验室本项目利用首次建立的自然突变维生素C缺陷模型-SFX小鼠，实验观察发现突变维生素C缺陷小鼠骨密度与正常有明显变化差异，维生素C在当前骨质疏松症的综合防治中可能发挥更大作用。为了弄清维生素C调节骨骼发育的最佳剂量及其影响骨密度的确切分子作用机制，本项目利用首次建立的自然突变维生素C缺陷模型-SFX小鼠、采用基因表达芯片技术从系统生物学角度动态分析维生素C对小鼠早期股骨发育（7-42天）中基因表达谱的影响、找到维生素C在小鼠早期骨骼发育中的调控网络，发现骨密度存在性别差异；维生素C干预前后小鼠股骨基因表达谱存在差异；确立维生素C最佳剂量；并进行维生素C的替代治疗，为临床合理使用维生素C防治骨质疏松症提供科学依据。