因作用机制未明，既往认为I型胶原是一种结构蛋白而难以决定细胞命运；事实上它是骨吸收与骨形成的主要有机成分，能包裹成骨细胞（OB）并为骨细胞分化所必须；最近其受体OSCAR的发现为它启动细胞内信号转导并决定细胞命运提供了依据；我们进一步研究发现：I型胶原能促进OB向骨细胞转化，初步证实成骨谱系细胞表达OSCAR，二者结合的受体后信号可能参与了OB向骨细胞转化以及破骨细胞的形成。本研究拟通过三维旋转培养模拟体内OB向骨细胞分化的不同阶段，检测胶原受体的表达规律并设计活性胶原肽；再分别用OB以及骨细胞特异性OSCAR剔除小鼠来确认I型胶原调节细胞分化的受体特异性；骨细胞突触与转录因子PCR阵列、通路信号分子特异性阻滞或恢复来探讨胶原与OSCAR结合后的受体后信号通路，最终验证我们的假设：I型胶原通过受体OSCAR调节前骨细胞分化与破细胞形成参与骨重建，并考察I型胶原多肽在骨质疏松中的应用价值。

Collagen type I is widely used in our daily life and research, but it was usually looked as a structural protein although 90% of the bone matrix are collagens type I. Recently, the receptor of collagen in osteoclast, osteoclast-associated receptor (OSCAR), was found to bind to specific motifs within fibrillar collagens，then initiated the important signal pathway in cell growth,differentiation and activity. In our previously study, we found that collagen type I promoted the differentiation of osteoblasts into osteocytes, and enhanced the activities of osteoclasts. In this study, we will mimic the different phase of the differentiation of osteocytes through the contorted three-dimensional cell culture in vitro, analyze the expression of OSCAR in osteoblast, pre-osteocytes and osteocytes. Then we will validate the receptor-specifically regulation of collagen in cell differentiation by conditional OSCAR knock-out mice in osteoblast and osteocyte respectively, and discover the involved signal pathway after collagens type I binding to its' receptor OSCAR by synapses specific PCR array and transcription factors PCR array analysis, and also by inhibiting or recovering the related signal moleculars in the signal transductional pathway. The aim of the above mentioned studies was to validate our hypothesis: collagen type I regulates the bone remodeling through controlling the differentiation of pre-osteocyte and osteoclastogenesis by binding to it's receptor OSCAR. Finally, we will evaluate the potential roles of collagen type I peptides in the therapy of osteoporosis.