成骨细胞何时、何因被激活分化、趋化移行到骨吸收陷窝表面启动骨形成，是骨重建理论中未知的难题，也是突破促成骨药物开发桎梏的基础。从骨吸收后期到成骨细胞移行至骨吸收陷窝表面，骨代谢降解产物及相关细胞因子是骨重建微环境中的最大变量，也是解决这一难题的关键线索，我们前期已发现其中的Ⅰ型胶原降/水解多肽在骨重建中发挥重要作用；本研究将进一步发掘真实骨吸收微环境中的全部Ⅰ型胶原活性多肽，再利用三维培养、成骨细胞阶段特异性LAIR-1/OSCAR条件性基因剔除小鼠，研究其与受体结合并经SLIT3、PLCγ-Ca2+等通路，阶段特异性调控与趋化成骨谱系细胞，启动骨吸收陷窝内骨形成的机制；设计合成靶向骨组织的Ⅰ型胶原活性多肽并证实其促骨形成作用，分析体液中目标多肽与临床表型相关性；以此证实我们的假说：骨吸收微环境中Ⅰ型胶原水解活性多肽可促进成骨谱系细胞成熟趋化移行至骨吸收陷窝启动骨形成；同时研究其应用价值。

Exploring when and how osteoblasts are activated and differentiated, and recruiting to the bone resorption lacuna surface to initiate bone formation is a major issue in bone remodeling and the key to breaking through the current shackle of osteogenic-promoting drugs. From the late stage of bone resorption to the migration of osteoblasts to the surface of bone resorption lacuna, degradation products and related cytokines from bone tissue are the largest variables in the bone remodeling microenvironment and a source of signal for explaining this problem; among them SLIT3 and collagen degradation peptides have been confirmed by us and other scholars that they play an important role in the osteogenesis stage of bone remodeling. In this study we will identify the active collagen polypeptide profile in the real bone resorption microenvironment. We will use three-dimensional culture, and osteoblast stage-specific LAIR-1/OSCAR knockout mice to study their binding to receptors via SLIT3, PLCγ-Ca2+ and other pathways to stage-specific regulate and chemotax osteogenic lineage cells and initiate the bone formation in the absorbing lacuna. Then we will target the bone cells by linking the polypeptide to the (Asp)8 to promote bone formation specifically, and analyze the correlation of target polypeptides levels in the body fluid with the clinical phenotype of osteoporosis. The aim of the above mentioned studies was to validate our hypothesis: Type I collagen degradation active polypeptide in bone resorption microenvironment can promote chemotaxis of osteogenic lineage cell to bone resorption lacuna to initiate bone formation, and clarify its mechanism and application.