[en] [en] 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.
Disciplines :
Food science Chemistry
Author, co-author :
Qi, Liwei; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Zhang, Hongru ; Université de Liège - ULiège > TERRA Research Centre ; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Guo, Yujie; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Zhang, Chunhui ; Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
Xu, Yang; Inner Mongolia Mengtai Biological Engineering Co., Ltd., Shengle Economic Park, Helinger County, Hohhot, Inner Mongolia, 010000, China
Language :
English
Title :
Novel Calcium-Binding Peptide from Bovine Bone Collagen Hydrolysates and Its Potential Pro-Osteogenic Activity via Calcium-Sensing Receptor (CaSR).
This work was supported by the Technical breathrough projects of Inner Mongolia science and technology Program (2022JBGS0007); National Agricultural Science and Technology Innovation Project (CAAS‐ASTIP‐2023).
J. Li, X. Chen, L. Lu, X. Yu, Cytokine Growth Factor Rev. 2020, 52, 88.
X. Cheng, K. Zhao, X. Zha, X. Du, Y. Li, S. Chen, Y. Wu, S. Li, Y. Lu, Y. Zhang, X. Xiao, Y. Li, X. Ma, X. Gong, W. Chen, Y. Yang, J. Jiao, B. Chen, Y. Lv, J. Gao, G. Hong, Y. Pan, Y. Yan, H. Qi, L. Ran, J. Zhai, L. Wang, K. Li, H. Fu, J. Wu, et al., J. Bone Miner. Res. 2021, 36, 427.
M. A. Kacena, C. M. Gundberg, M. C. Horowitz, Bone 2006, 39, 978.
K. Dashnyam, O. Bayaraa, N. Mandakhbayar, J.-H. Park, J.-H. Lee, T-Su Jang, K. Luvsan, H.-W. Kim, ACS Biomater. Sci. Eng. 2020, 6, 4604.
J. B. Lian, G. S. Stein, Iowa Orthop. J. 1995, 15, 118.
C. Cao, Y. Ren, A. S. Barnett, A. J. Mirando, D. Rouse, Se H Mun, K.-H. Park-Min, A. L. Mcnulty, F. Guilak, C. M. Karner, M. J. Hilton, G. S. Pitt, JCI Insight 2017, 2, 22.
C. Wang, D. Zhang, M. Zhang, Y. Jiao, K. Jiang, C. Yan, Ind. Crops Prod. 2017, 108, 458.
C. Yan, S. Zhang, C. Wang, Q. Zhang, Carbohydr. Polym. 2019, 210, 110.
M. Zhang, Y. Wang, Q. Zhang, C. Wang, D. Zhang, J.-B. Wan, C. Yan, Int. J. Biol. Macromol. 2018, 112, 433.
W. Wu, L. He, Y. Liang, L. Yue, W. Peng, G. Jin, M. Ma, Food Chem. 2019, 284, 80.
Y. Lin, X. Cai, X. Wu, S. Lin, S. Wang, J. Funct. Foods 2020, 65, 103717.
H. Xiang, H. Huang, D. Sun-Waterhouse, X. Hu, L. Li, G. I. N. Waterhouse, R. Tang, J. Xiong, C. Cui, Food Chem. 2022, 387, 132918.
Na Sun, S. Hu, Di Wang, P. Jiang, S. Zhang, S. Lin, J. Agric. Food Chem. 2022, 70, 2018.
E. M. Brown, Best Pract. Res. Clin. Endocrinol. Metab. 2013, 27, 333343.
S. Tharmalingam, D. R. Hampson, Front. Physiol. 2016, 7, 190.
Y. Miao, Q. Shen, S. Zhang, H. Huang, F. Zou, Breast Cancer Res. 2019, 21, 99.
H. Yuan, Y. Fan, Y. Wang, T. Gao, C. Wei, Mol. Med. Rep. 2019, 20, 1093.
T. Matsunobu, K. Torigoe, M. Ishikawa, S. De Vega, A. B. Kulkarni, Y. Iwamoto, Y. Yamada, Dev. Biol. 2009, 332, 325.
S. Ling, P. Shi, S. Liu, X. Meng, Y. Zhou, W. Sun, S. Chang, X. Zhang, L. Zhang, C. Shi, D. Sun, L. Liu, C. Tian, Cell Res. 2021, 31, 383.
Y. Geng, L. Mosyak, I. Kurinov, H. Zuo, E. Sturchler, T. C. Cheng, P. Subramanyam, A. P. Brown, S. C. Brennan, H.-C. Mun, M. Bush, Y. Chen, T. X. Nguyen, B. Cao, D. D. Chang, M. Quick, A. D. Conigrave, H. M. Colecraft, P. McDonald, Q. R. Fan, Elife 2016, 5, 13662.
D. Guo, H. He, T. Hou, Food Chem. 2020, 325, 126919.
S. C. Hebert, S. Cheng, J. Geibel, Cell Calcium 2004, 35, 239.
A. Malison, P. Arpanutud, S. Keeratipibul, Food Chem. 2021, 345, 128713.
Da Chen, Z. Liu, W. Huang, Y. Zhao, S. Dong, M. Zeng, J. Funct. Foods 2013, 5, 689.
C. Zhang, T. Zhang, J. Zou, C. L. Miller, R. Gorkhali, J.-Y. Yang, A. Schilmiller, S. Wang, K. Huang, E. M. Brown, K. W. Moremen, J. Hu, J. J. Yang, Sci. Adv. 2016, 2, e1600241.
L. Guo, P. A. Harnedy, B. Li, H. Hou, Z. Zhang, X. Zhao, R. J. FitzGerald, Trends Food Sci. Technol. 2014, 37, 92.
L. Zhao, Q. Huang, S. Huang, J. Lin, S. Wang, Y. Huang, J. Hong, P. Rao, J. Agric. Food Chem. 2014, 62, 10274.
R. P. Houser, M. P. Fitzsimons, J. K. Barton, Inorg. Chem. 1999, 38, 1368.
A. Armas, V. Sonois, E. Mothes, H. Mazarguil, P. Faller, J. Inorg. Biochem. 2006, 100, 1672.
X. Zhang, J. A. Arnott, S. Rehman, W. G. Delong, A. Sanjay, F. F. Safadi, S. N. Popoff, J. Cell. Physiol. 2010, 224, 691.
A. Hassani, A. B. Khoshfetrat, R. Rahbarghazi, S. Sakai, Carbohydr. Polym. 2021, 277, 118807.
A. Hassani, Ç. B. Avci, S. N. Kerdar, H. Amini, M. Amini, M. Ahmadi, S. Sakai, B. G. Bagca, N. P. Ozates, R. Rahbarghazi, A. B. Khoshfetrat, J. Nanobiotechnol. 2022, 20, 310.
A. L. Magno, B. K. Ward, T. Ratajczak, Endocr. Rev. 2011, 32, 3.
A. N. Keller, I. Kufareva, T. M. Josephs, J. Diao, V. T. Mai, A. D. Conigrave, A. Christopoulos, K. J. Gregory, K. Leach, Mol. Pharmacol. 2018, 93, 619.
C. L. Miller, R. Gorkhali, J. Zou, K. Huang, E. M. Brown, J. J. Yang, Front. Physiol. 2016, 7, 441.
A. V. Taubenberger, M. A. Woodruff, H. Bai, D. J. Muller, D. W. Hutmacher, Biomaterials 2010, 31, 2827.
W. Wu, L. He, C. Li, S. Zhao, Y. Liang, F. Yang, M. Zhang, G. Jin, M. Ma, J. Funct. Foods 2020, 64, 103701.
W. Peng, W. Deng, J. Zhang, G. Pei, Q. Rong, S. Zhu, Biochem. Biophys. Res. Commun. 2018, 503, 815.
S. Mohamed-Ahmed, I. Fristad, S. Atle Lie, S. Suliman, K. Mustafa, H. Vindenes, S. B. Idris, Stem Cell Res. Ther. 2018, 9, 168.
J. Tang, Z. Zhang, X. Jin, H. Shi, Bone 2018, 114, 137.
Y.-Y. Kong, H. Yoshida, I. Sarosi, H.-L. Tan, E. Timms, C. Capparelli, S. Morony, A. J. Oliveira-Dos-Santos, G. Van, A. Itie, W. Khoo, A. Wakeham, C. R. Dunstan, D. L. Lacey, T. W. Mak, W. J. Boyle, J. M. Penninger, Nature 1999, 397, 315.
R. R. Kelly, L. T. Mcdonald, V. D. Pellegrini, J. J. Cray, A. C. Larue, Cytotherapy 2018, 20, 1371.
