Novel Calcium‐Binding Peptide from Bovine Bone Collagen Hydrolysates and Its Potential Pro‐Osteogenic Activity via Calcium‐Sensing Receptor (CaSR)

化学 生物学中的钙 受体 钙敏感受体 碱性磷酸酶 信号转导 骨钙素 细胞生物学 生物化学 内科学 内分泌学 钙代谢 生物 医学 有机化学
作者
Liwei Qi,Hongru Zhang,Yujie Guo,Chunhui Zhang,Yang Xu
出处
期刊:Molecular Nutrition & Food Research [Wiley]
卷期号:68 (4)
标识
DOI:10.1002/mnfr.202200726
摘要

Scope This paper aims to explore the osteogenic activity and potential mechanism of the peptide‐calcium chelate, and provides a theoretical basis for peptide‐calcium chelates as functional foods to prevent or improve osteoporosis. Methods and results In this research, a novel peptide (Phe‐Gly‐Leu, FGL) with a high calcium‐binding capacity is screened from bovine bone collagen hydrolysates (CPs), calcium binding sites of which mainly included carbonyl, amino and carboxyl groups. The FGL‐Ca significantly enhances the osteogenic activity of MC3T3‐E1 cells (survival rate, differentiation, and mineralization). The results of calcium fluorescence labeling and molecular docking show that FGL‐Ca may activate calcium‐sensing receptor (CaSR), leading to an increase in intracellular calcium concentration, then enhancing osteogenic activity of MC3T3‐E1 cells. Further research found that FGL‐Ca significantly promotes the mRNA and protein expression levels of CaSR, transforming growth factor β (TGF‐β1), TGF‐β‐type II receptor (TβRII), Smad2, Smad3, osteocalcin (OCN), alkaline phosphatase (ALP), osteoprotegrin (OPG), and collagen type I (COLI). Subsequently, in the signal pathway intervention experiment, the expression levels of genes and proteins related to the TGF‐β1/Smad2/3 signaling pathway that are promoted by FGL‐Ca are found to decrease. Conclusions These results suggest that FGL‐Ca may activate CaSR, increase intracellular calcium concentration, and activate TGF‐β1/Smad2/3 signaling pathway, which may be one of the potential mechanisms for enhancing osteogenic activity.
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