Fish bone peptide promotes osteogenic differentiation of MC3T3-E1 pre-osteoblasts through upregulation of MAPKs and Smad pathways activated BMP-2 receptor

Cell Biochem Funct. 2018 Apr;36(3):137-146. doi: 10.1002/cbf.3325. Epub 2018 Feb 1.

Abstract

Fish bone, a by-product of fishery processing, is composed of protein, calcium, and other minerals. The objective of this study was to investigate the effects of a bioactive peptide isolated from the bone of the marine fish, Johnius belengerii, on the osteoblastic differentiation of MC3T3-E1 pre-osteoblasts. Post consecutive purification by liquid chromatography, a potent osteogenic peptide, composed of 3 amino acids, Lys-Ser-Ala (KSA, MW: 304.17 Da), was identified. The purified peptide promoted cell proliferation, alkaline phosphatase activity, mineral deposition, and expression levels of phenotypic markers of osteoblastic differentiation in MC3T3-E1 pre-osteoblast. The purified peptide induced phosphorylation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase, extracellular regulated kinase, and c-Jun N-terminal kinase as well as Smads. As attested by molecular modelling study, the purified peptide interacted with the core interface residues in bone morphogenetic protein receptors with high affinity. Thus, the purified peptide could serve as a potential pharmacological substance for controlling bone metabolism.

Keywords: Johnius belengerii; Smad 1/5/8; alkaline phosphatase (ALP); mitogen-activated protein kinases (MAPKs); osteoblast differentiation.

MeSH terms

  • 3T3 Cells
  • Animals
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone and Bones / chemistry*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Fish Proteins / isolation & purification
  • Fish Proteins / pharmacology*
  • Gadiformes
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Molecular
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects*
  • Smad Proteins / metabolism*
  • Up-Regulation / drug effects

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Fish Proteins
  • Smad Proteins
  • Mitogen-Activated Protein Kinases