College of Life Science, Yantai University, Yantai 264000, China.
Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Nutrients. 2022 May 5;14(9):1940. doi: 10.3390/nu14091940.
DEDEQIPSHPPR, the calcium-binding peptide (CBP) identified in soy yogurt, was proven to be a potential cofactor in osteoporosis prevention in our previous study, but the mechanism was unknown. In this study, the activity of alkaline phosphatase (ALP) and osteocalcin (OCN), the regulation of RUNX2, and the expression of TβRI were investigated to elucidate the underlying mechanism. The results show that CBP upregulated ALP activity and OCN concentration and increased the expression of RUNX2 and the activation of the MAPK signaling pathway. Similarly, the expression of osteogenesis-related genes in osteoblasts also increased upon CBP treatment. Moreover, the CBP-induced enhancement of ALP activity and phosphorylation levels in the p38 pathway was inhibited by treatment with a p38 inhibitor (SB203538) and TβRI inhibitor (SB431542), respectively, suggesting that p38 and TβRI were involved in the osteogenic action. Based on the signaling pathways, the intracellular calcium concentration was significantly elevated by CBP, which was correlated with the increased behavioral functions and the relative fluorescence intensity of the bone mass. These findings suggest that CBP stimulates osteoblast differentiation and bone mineralization through the activation of RUNX2 via mechanisms related to the TβRI-p38-MAPK signaling pathways, further highlighting CBP's important potential for treating osteoporosis.
DEDEQIPSHPPR 是在大豆酸奶中发现的钙结合肽（CBP），在我们之前的研究中已被证明是预防骨质疏松症的潜在辅助因子，但具体机制尚不清楚。在这项研究中，我们研究了碱性磷酸酶（ALP）和骨钙素（OCN）的活性、RUNX2 的调控以及 TβRI 的表达，以阐明其潜在的机制。结果表明，CBP 可上调 ALP 活性和 OCN 浓度，并增加 RUNX2 的表达和 MAPK 信号通路的激活。同样，CBP 处理后成骨细胞中成骨相关基因的表达也增加。此外，用 p38 抑制剂（SB203538）和 TβRI 抑制剂（SB431542）分别处理可抑制 CBP 诱导的 ALP 活性和 p38 通路磷酸化水平的增强，提示 p38 和 TβRI 参与了成骨作用。基于信号通路，CBP 显著提高了细胞内钙浓度，这与行为功能的增强和骨量的相对荧光强度有关。这些发现表明，CBP 通过与 TβRI-p38-MAPK 信号通路相关的机制激活 RUNX2 来刺激成骨细胞分化和骨矿化，进一步强调了 CBP 在治疗骨质疏松症方面的重要潜力。
