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Collagen Peptide Upregulates Osteoblastogenesis from Bone Marrow Mesenchymal Stem Cells through MAPK- Runx2

Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China
Department of Fish Quality Assurance and Management, Fish Quality Monitoring and Certification Centre, Fisheries College and Research Institute, Tamil Nadu Dr.J.Jayalalitha Fisheries University, Tuticorin 628008, India
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, 14513 Teltow, Germany
Institute of Chemistry and Biochemistry, Free university Berlin, 14195 Berlin, Germany
Department of Biomaterials Engineering, Universidad Católica San Antonio de Murcia, 30107 Murcia, Spain
Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation, Ministry of Agriculture, Shanghai 201306, China
Author to whom correspondence should be addressed.
Cells 2019, 8(5), 446;
Received: 30 March 2019 / Revised: 6 May 2019 / Accepted: 9 May 2019 / Published: 11 May 2019
(This article belongs to the Special Issue Extracellular Matrix Remodeling 2019)
PDF [4255 KB, uploaded 11 May 2019]


Collagen is the most abundant extracellular fibrous protein that has been widely used for biomedical applications due to its excellent biochemical and biocompatibility features. It is believed that the smaller molecular weight collagen, i.e., collagen peptide (CP), has more potent activity than native collagen. However, the preparation of CP from fish bone collagen is a complex and time-consuming process. Additionally, the osteogenic effect of CP depends on its molecular weight and amino acid composition. Considering the above concept, the present work was undertaken to extract the CP directly from Mahi mahi fish (Coryphaena hippurus) bones and test its osteogenic potential using bone marrow mesenchymal stem (BMMS) cells. The hydrolyzed collagen contained triple alpha chains (110 kDa) and a peptide (~1 kDa) and the peptide was successfully separated from hydrolyzed collagen using molecular weight cut-off membrane. CP treatment was up-regulated BMMS cells proliferation and differentiation. Interestingly, CP accrued the mineral deposition in differentiated BMMS cells. Protein and mRNA expression revealed that the osteogenic biomarkers such as collagen, alkaline phosphatase, and osteocalcin levels were significantly increased by CP treatment in differentiated BMMS cells and also further elucidated the hypothesis that CP was upregulated osteogenesis through activating Runx2 via p38MAPK signaling pathway. The above results concluded that the CP from Mahi mahi bones with excellent osteogenic properties could be the suitable biomaterial for bone therapeutic application. View Full-Text
Keywords: collagen peptide; Mahi mahi; mesenchymal stem cell; differentiation; p38MAPK; mineral deposition; Runx2 collagen peptide; Mahi mahi; mesenchymal stem cell; differentiation; p38MAPK; mineral deposition; Runx2

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Elango, J.; Robinson, J.; Zhang, J.; Bao, B.; Ma, N.; de Val, J.E.M.S.; Wu, W. Collagen Peptide Upregulates Osteoblastogenesis from Bone Marrow Mesenchymal Stem Cells through MAPK- Runx2. Cells 2019, 8, 446.

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