骨钙素在骨骼与其它组织器官间的交互调控是近来生物医学研究的热点，然骨钙素在骨代谢平衡调节中的作用依然存在很大争议，其关键是骨钙素存在羧化和非羧化两种形式，它们在骨重建过程中具体作用尚不清晰。基于当前非羧化骨钙素功能的挖掘和我们前期研究发现，发展基于CRTSPR系统的组织特异性基因敲除技术，构建骨钙素基因敲除和分泌非羧化骨钙素的动物和细胞模型，采用microCT、三点弯曲法、qRT-PCR、组织化学染色等方法，在动物整体、组织器官和细胞分子水平，从骨骼生长发育、力学响应重建过程、成骨细胞活性和功能、破骨细胞分化成熟、成骨和破骨细胞交互调控等方面，研究羧化和非羧化骨钙素对骨重建平衡的骨形成和骨吸收的影响，旨在阐明羧化和非羧化骨钙素在骨重建过程中的作用及其可能的机制；为证实羧化和非羧化这种生理系统新的调节模式的假说奠定坚实的理论基础。

Osteocalcin plays a vital role in the crosstalk between bone and other tissues, which is becoming a focus of the biomedical research. But the exact function of osteocalcin in the balance regulation of bone metabolism is still controversial. The major reason is that there are two forms of osteocalcin (carboxylated and undercarboxylated) and their function during bone remodeling is far from clear. Based on recent reports and our newest research results of undercarboxylated osteocalcin, we plan to develop a tissue specific gene knockout technique on the basis of CRISPR system; construct animal and cell models that knock out osteocalcin gene cluster or specifically secret undercarboxylated osteocalcin. MicroCT, three-point bending biomechanic analysis, RT-qPCR and histochemical stain will be used to study the role of carboxylated and undercarboxylated osteocalcin in bone remodeling balance between bone formation and resorption including bone development as whole, mechanical response to unloading conditions, activity and function of osteoblast, differentiation and maturity of osteoclast, and the mutual regulation between osteoblast and osteoclast. We aim to clarify the exact function and mechanism of carboxlated and undercarboxylated osteocalcin in bone remodeling process, which will provide theoretical basis for the hypothesis that carboxylation and undercarboxylation is a new regulation model for physiology system.