Xu Zihan, Yang Chao, Wu Feng, Tan Xiaowen, Guo Yaxiu, Zhang Hongyu, Wang Hailong, Sui Xiukun, Xu Zi, Zhao Minbo, Jiang Siyu, Dai Zhongquan, Li Yinghui
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
Front Physiol. 2023 Mar 28;14:1136561. doi: 10.3389/fphys.2023.1136561. eCollection 2023.
Osteocalcin (Ocn), also known as bone Gla protein, is synthesized by osteoblasts and thought to regulate energy metabolism, testosterone synthesis and brain development. However, its function in bone is not fully understood. Mice have three Ocn genes: Bglap, Bglap2 and Bglap3. Due to the long span of these genes in the mouse genome and the low expression of Bglap3 in bone, researchers commonly use Bglap and Bglap2 knockout mice to investigate the function of Ocn. However, it is unclear whether Bglap3 has any compensatory mechanisms when Bglap and Bglap2 are knocked out. Considering the controversy surrounding the role of Ocn in bone, we constructed an Ocn-deficient mouse model by knocking out all three genes (Ocn) and analyzed bone quality by Raman spectroscopy (RS), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and MicroCT (μCT). The RS test showed that the alignment of hydroxyapatite crystals and collagen fibers was significantly poorer in Ocn mice than in wild-type (WT) mice. Ocn deficiency resulted in a looser surface structure of bone particles and a larger gap area proportion. FTIR analysis showed few differences in bone mineral index between WT and Ocn mice, while μCT analysis showed no significant difference in cortical and trabecular regions. However, under tail-suspension simulating bone loss condition, the disorder of hydroxyapatite and collagen fiber alignment in Ocn mice led to more obvious changes in bone mineral composition. Collectively, our results revealed that Ocn is necessary for regulating the alignment of minerals parallel to collagen fibrils.
骨钙素（Ocn），也被称为骨γ-羧基谷氨酸蛋白，由成骨细胞合成，被认为可调节能量代谢、睾酮合成和大脑发育。然而，其在骨骼中的功能尚未完全明确。小鼠有三个Ocn基因：Bglap、Bglap2和Bglap3。由于这些基因在小鼠基因组中的跨度较长，且Bglap3在骨骼中的表达较低，研究人员通常使用Bglap和Bglap2基因敲除小鼠来研究Ocn的功能。然而，尚不清楚当Bglap和Bglap2被敲除时，Bglap3是否具有任何补偿机制。考虑到围绕Ocn在骨骼中作用的争议，我们通过敲除所有三个基因（Ocn）构建了一个Ocn缺陷小鼠模型，并通过拉曼光谱（RS）、扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）和显微计算机断层扫描（μCT）分析了骨质量。RS测试表明，Ocn小鼠中羟基磷灰石晶体和胶原纤维的排列明显比野生型（WT）小鼠差。Ocn缺乏导致骨颗粒表面结构更松散，间隙面积比例更大。FTIR分析显示WT小鼠和Ocn小鼠之间的骨矿物质指数几乎没有差异，而μCT分析显示皮质和小梁区域没有显著差异。然而，在模拟骨质流失情况的尾部悬吊条件下，Ocn小鼠中羟基磷灰石和胶原纤维排列紊乱导致骨矿物质组成发生更明显的变化。总的来说，我们的结果表明，Ocn对于调节矿物质与胶原纤维平行排列是必要的。
