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In Vitro and In Vivo Bone-Forming Effect of a Low-Molecular-Weight Collagen Peptide

  • Jae Min Hwang (Health Food Research and Development, NEWTREE Co., Ltd.) ;
  • Mun-Hoe Lee (Health Food Research and Development, NEWTREE Co., Ltd.) ;
  • Yuri Kwon (Health Food Research and Development, NEWTREE Co., Ltd.) ;
  • Hee-Chul Chung (Health Food Research and Development, NEWTREE Co., Ltd.) ;
  • Do-Un Kim (Health Food Research and Development, NEWTREE Co., Ltd.) ;
  • Jin-Hee Lee (Health Food Research and Development, NEWTREE Co., Ltd.)
  • Received : 2023.07.14
  • Accepted : 2023.11.09
  • Published : 2024.02.28

Abstract

This study reveals that low-molecular-weight collagen peptide (LMWCP) can stimulate the differentiation and the mineralization of MC3T3-E1 cells in vitro and attenuate the bone remodeling process in ovariectomized (OVX) Sprague-Dawley rats in vivo. Moreover, the assessed LMWCP increased the activity of alkaline phosphatase (ALP), synthesis of collagen, and mineralization in MC3T3-E1 cells. Additionally, mRNA levels of bone metabolism-related factors such as the collagen type I alpha 1 chain, osteocalcin (OCN), osterix, bone sialoprotein, and the Runt family-associated transcription factor 2 were increased in cells treated with 1,000 ㎍/ml of LMWCP. Furthermore, we demonstrated that critical bone morphometric parameters exhibited significant differences between the LMWCP (400 mg/kg)-receiving and vehicle-treated rat groups. Moreover, the expression of type I collagen and the activity of ALP were found to be higher in both the femur and lumbar vertebrae of OVX rats treated with LMWCP. Finally, the administration of LMWCP managed to alleviate osteogenic parameters such as the ALP activity and the levels of the bone alkaline phosphatase, the OCN, and the procollagen type 1 N-terminal propeptide in OVX rats. Thus, our findings suggest that LMWCP is a promising candidate for the development of food-based prevention strategies against osteoporosis.

Keywords

Acknowledgement

This work was supported by NEWTREE Co., Ltd., Korea.

References

  1. Min G. 2017. Collagen hydrolysate Gly-Pro-Hyp on osteoblastic proliferation and differentiation of MC3T3-E1 cells. J. Clin. Nurs. Res. 1. 10.26689/jcnr.v1i3.158.
  2. Lim SY, Bolster MB. 2015. Current approaches to osteoporosis treatment. Curr. Opin. Rheumatol. 27: 216-224.
  3. Sequeira L, Nguyen J, Wang L, Nohe A. 2020. A novel peptide, ck2.3, improved bone formation in ovariectomized Sprague Dawley rats. Int. J. Mol. Sci. 21: 4874.
  4. Lin X, Patil S, Gao YG, Qian A. 2020. The bone extracellular matrix in bone formation and regeneration. Front. Pharmacol. 11: 757.
  5. Leon-Lopez A, Morales-Penaloza A, Martinez-Juarez VM, Vargas-Torres A, Zeugolis DI, Aguirre-Alvarez G. 2019. Hydrolyzed collagen-sources and applications. Molecules 24: 4031.
  6. de Miranda RB, Weimer P, Rossi RC. 2021. Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis. Int. J. Dermatol. 60: 1449-1461.
  7. Cuneo F, Costa-Paiva L, Pinto-Neto AM, Morais SS, Amaya-Farfan J. 2010. Effect of dietary supplementation with collagen hydrolysates on bone metabolism of postmenopausal women with low mineral density. Maturitas 65: 253-257.
  8. Konig D, Oesser S, Scharla S, Zdzieblik D, Gollhofer A. 2018. Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women-a randomized controlled study. Nutrients 10: 97.
  9. Hata S, Hayakawa T, Okada H, Hayashi K, Akimoto Y, Yamamoto H. 2008. Effect of oral administration of high advanced-collagen tripeptide (HACP) on bone healing process in rat. J. Hard Tissue Biol. 17: 17-22.
  10. Tsuruoka N, Yamato R, Sakai Y, Yoshitake Y, Yonekura H. 2007. Promotion by collagen tripeptide of type I collagen gene expression in human osteoblastic cells and fracture healing of rat femur. Biosci. Biotechnol. Biochem. 71: 2680-2687.
  11. Liu C, Sun J. 2014. Potential application of hydrolyzed fish collagen for inducing the multidirectional differentiation of rat bone marrow mesenchymal stem cells. Biomacromolecules 15: 436-443.
  12. Guillerminet F, Fabien-Soule V, Even PC, Tome D, Benhamou CL, Roux C, et al. 2012. Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice. Osteoporos. Int. 23: 1909-1919.
  13. Han X, Xu Y, Wang J, Pei X, Yang R, Li N, et al. 2009. Effects of cod bone gelatin on bone metabolism and bone microarchitecture in ovariectomized rats. Bone 44: 942-947.
  14. Kamikura K, Minatoya T, Terada-Nakaishi M, Yamamoto S, Sakai Y, Furusawa T, et al. 2017. Enhanced bone formation in the vicinity of porous beta-TCP scaffolds exhibiting slow release of collagen-derived tripeptides. J. Mater. Sci. Mater. Med. 28: 132.
  15. Kim DU, Chung HC, Choi J, Sakai Y, Lee BY. 2018. Oral intake of low-molecular-weight collagen peptide improves hydration, elasticity, and wrinkling in human skin: a randomized, double-blind, placebo-controlled study. Nutrients 10: 826.
  16. Kim JK. 2009. Beneficial effect of collagen peptide supplement on anti-aging against photodamage. Korean J. Food Sci. Technol. 41: 441-445.
  17. Okawa T, Yamaguchi Y, Takada S, Sakai Y, Numata N, Nakamura F, et al. 2012. Oral administration of collagen tripeptide improves dryness and pruritus in the acetone-induced dry skin model. J. Dermatol. Sci. 66: 136-143.
  18. Lee MH, Kim HM, Chung HC, Kim DU, Lee JH. 2021. Low-molecular-weight collagen peptide ameliorates osteoarthritis progression through promoting extracellular matrix synthesis by chondrocytes in a rabbit anterior cruciate ligament transection model. J. Microbiol. Biotechnol. 31: 1401-1408.
  19. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. 2010. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J. Bone Miner. Res. 25: 1468-1486.
  20. Zhang H, Shi X, Wang L, Li X, Zheng C, Gao B, et al. 2018. Intramembranous ossification and endochondral ossification are impaired differently between glucocorticoid-induced osteoporosis and estrogen deficiency-induced osteoporosis. Sci. Rep. 8: 3867.
  21. Li W, Zhang S, Liu J, Liu Y, Liang Q. 2019. Vitamin K2 stimulates MC3T3-E1 osteoblast differentiation and mineralization through autophagy induction. Mol. Med. Rep. 19: 3676-3684.
  22. Bhargavan B, Gautam AK, Singh D, Kumar A, Chaurasia S, Tyagi AM, et al. 2009. Methoxylated isoflavones, cajanin and isoformononetin, have non-estrogenic bone forming effect via differential mitogen activated protein kinase (MAPK) signaling. J. Cell. Biochem. 108: 388-399.
  23. Maeda T, Matsunuma A, Kawane T, Horiuchi N. 2001. Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem. Biophys. Res. Commun. 280: 874-877.
  24. Lubec G, Labudova O, Seebach D, Beck A, Hoeger H, Hermon M, et al. 1995. Alpha-methyl-proline restores normal levels of bone collagen type I synthesis in ovariectomized rats. Life Sci. 57: 2245-2252.
  25. Sinha KM, Zhou X. 2013. Genetic and molecular control of osterix in skeletal formation. J. Cell. Biochem. 114: 975-984.
  26. Wang D, Christensen K, Chawla K, Xiao G, Krebsbach PH, Franceschi RT. 1999. Isolation and characterization of MC3T3-E1 preosteoblast subclones with distinct in vitro and in vivo differentiation/mineralization potential. J. Bone Miner. Res. 14: 893-903.
  27. Liu J, Wang Y, Song S, Wang X, Qin Y, Si S, et al. 2015. Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats. PLoS One 10: e0135019.
  28. Stein GS, Lian JB. 1993. Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr. Rev. 14: 424-442.
  29. Kim HK, Kim MG, Leem KH. 2013. Osteogenic activity of collagen peptide via ERK/MAPK pathway mediated boosting of collagen synthesis and its therapeutic efficacy in osteoporotic bone by back-scattered electron imaging and microarchitecture analysis. Molecules 18: 15474-15489.
  30. Li B. 2017. Beneficial effects of collagen hydrolysate: a review on recent developments. Biomed. J. Sci. Tech. Res 1. DOI: 10.26717/BJSTR.2017.01.000217.
  31. Bello AE, Oesser S. 2006. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature. Curr. Med. Res. Opin. 22: 2221-2232.
  32. Daneault A, Prawitt J, Fabien Soule VF, Coxam V, Wittrant Y. 2017. Biological effect of hydrolyzed collagen on bone metabolism.Crit. Rev. Food Sci. Nutr. 57: 1922-1937.
  33. Siddiqui S, Mahdi AA, Arshad M. 2020. Genistein contributes to cell cycle progression and regulates oxidative stress in primary culture of osteoblasts along with osteoclasts attenuation. BMC Complement. Med. Ther. 20: 277.
  34. Muthusami S, Senthilkumar K, Vignesh C, Ilangovan R, Stanley J, Selvamurugan N, et al. 2011. Effects of Cissus quadrangularis on the proliferation, differentiation and matrix mineralization of human osteoblast like SaOS-2 cells. J. Cell. Biochem. 112: 1035-1045.
  35. Seo HJ, Cho YE, Kim T, Shin HI, Kwun IS. 2010. Zinc may increase bone formation through stimulating cell proliferation, alkaline phosphatase activity and collagen synthesis in osteoblastic MC3T3-E1 cells. Nutr. Res. Pract. 4: 356-361.
  36. Liu L, Zhou L, Yang X, Liu Q, Yang L, Zheng C, et al. 2018. 17beta-estradiol attenuates ovariectomy-induced bone deterioration through the suppression of the ephA2/ephrinA2 signaling pathway. Mol. Med. Rep. 17: 1609-1616.
  37. Siddiqui S, Arshad M. 2014. Osteogenic potential of Punica granatum through matrix mineralization, cell cycle progression and runx2 gene expression in primary rat osteoblasts. Daru 22: 72.
  38. Kim HJ. 2004. Micro-structural profiles of trabecular bone at the ankle joint. J. Korean Foot Ankle Soc. 8: 157-160.
  39. Tantikanlayaporn D, Wichit P, Weerachayaphorn J, Chairoungdua A, Chuncharunee A, Suksamrarn A, et al. 2013. Bone sparing effect of a novel phytoestrogen diarylheptanoid from Curcuma comosa Roxb. in ovariectomized rats. PLoS One 8: e78739.
  40. Han J, Wang W. 2017. Effects of tanshinol on markers of bone turnover in ovariectomized rats and osteoblast cultures. PLoS One 12: e0181175.
  41. Rissanen JP, Suominen MI, Peng Z, Morko J, Rasi S, Risteli J, et al. 2008. Short-term changes in serum PINP predict long-term changes in trabecular bone in the rat ovariectomy model. Calcif. Tissue Int. 82: 155-161.
  42. Yazaki M, Ito Y, Yamada M, Goulas S, Teramoto S, Nakaya MA, et al. 2017. Oral ingestion of collagen hydrolysate leads to the transportation of highly concentrated gly-pro-hyp and its hydrolyzed form of pro-hyp into the bloodstream and skin. J. Agric. Food Chem. 65: 2315-2322.
  43. Shigemura Y, Iwai K, Morimatsu F, Iwamoto T, Mori T, Oda C, et al. 2009. Effect of prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skin. J. Agric. Food Chem. 57: 444-449.