Ⅱ型胶原是常见的结构蛋白，更是重要的信号调节分子，可能通过盘状结构域受体2（DDR2）和/或整合素α2β1对骨软骨发育进行调控。我们课题组发现了Ⅱ型胶原基因突变引起的新Ⅱ型胶原病，并构建相应突变小鼠模型，发现纯合突变的小鼠骨骼发育过程明显异常，提示Ⅱ型胶原对软骨内成骨具有未知却关键的调控作用。本研究拟从软骨内成骨的三个层面，对各效应蛋白序贯拮抗与激活，以考察Ⅱ型胶原对软骨内成骨的调控机制。包括：一、干细胞水平：明确Ⅱ型胶原和DDR2/整合素α2β1对间充质干细胞成软骨、成骨分化的调节作用；二、软骨细胞水平：明确Ⅱ型胶原和DDR2/整合素α2β1对软骨细胞成熟的调节作用；三、成骨生长板水平：明确Ⅱ型胶原和DDR2/整合素α2β1对生长板发育的调节作用。最终阐明Ⅱ型胶原对软骨内成骨的信号调节功能，为Ⅱ型胶原病的发病机制提供解释，为其防治措施提供新思路，也为Ⅱ型胶原材料的临床应用提供理论基础。

Not only an ordinary structural protein that Collagen Ⅱ is, but also an extraordinary signaling molecular. It is likely to modulate the development of bone and cartilage through interacting with DDR2 and/or Integrin α2β1. Previously we discovered a novel type Ⅱ collagenopathy caused by mutation of p.G1170S in COL2A1, and we constructed a mouse model for the mutation. We found the skeletal development was severely defected in homozygous mutated mouse, implying that Collagen Ⅱ have an unknown but important role in regulating the endochondral ossification. Here, by antagonizing/activating the Collagen Ⅱ, DDR2 and Integrin α2β1 sequentially, we plan a rigorous strategy to study the signaling effect of Collagen II throughout the three levels of the endochondral ossification. Firstly, we will study the effects of Collagen Ⅱ, DDR2 and Integrin α2β1 in regulating the chondrogenesis and osteogenesis of mesenchymal stem cells. Secondly, the effects of Collagen Ⅱ, DDR2 and Integrin α2β1 in regulating maturation of chondrocytes will be measured. Thirdly, we are going to have a look at the effects of Collagen Ⅱ, DDR2 and Integrin α2β1 in regulating development of the growth plate. Through these, we can manifest the signal transductional effect of Collagen Ⅱ in endochondral ossification, explaining the mechanism of type Ⅱ collagenopathy, and offering new perspectives in the treatment of the disease.