Abstract

Bone regeneration is an important issue in many situations, such as bone fracture and surgery. Umbilical cord mesenchymal stem cells (UC-MSCs) are promising cell sources for bone regeneration. Bone morphogenetic proteins and their bioactive peptides are biomolecules known to enhance the osteogenic differentiation of MSCs. However, fibrosis can arise during the development of implantable biomaterials. Therefore, it is important to control cell organization by enhancing osteogenic proliferation and differentiation and inhibiting fibroblast proliferation. Thus, we focused on the screening of such osteogenic-enhancing peptides. In the present study, we developed new peptide array screening platforms to evaluate cell proliferation and alkaline phosphatase activity in osteoblasts, UC-MSCs and fibroblasts. The conditions for the screening platform were first defined using UC-MSCs and an osteogenic differentiation peptide known as W9. Next, in silico screening to define the candidate peptides was carried out to evaluate the homology of 19 bone morphogenetic proteins. Twenty-five candidate 9-mer peptides were selected for screening. Finally, the screening of osteogenic-enhancing (osteogenic cell-selective proliferation and osteogenic differentiation) short peptide was carried out using the peptide array method, and three osteogenic-enhancing peptides were identified, confirming the validity of this screening.

Highlights

  • Bone formation and regeneration are necessary phenomena in situations such as fracture due to osteoporosis, cleft lip and palate (CLP) and surgery

  • Peptide No 11 showed significantly lower proliferation than that in the Blank (p < 0.05). These results indicate variation in proliferation because the peptides were derived from Bone morphogenetic proteins (BMPs) in each cell type and that several peptides, such as peptide No 2

  • These results indicate that several osteogenic differentiation peptides are derived from BMPs, and Toofidentify osteogenic-enhancing peptides

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Summary

Introduction

Bone formation and regeneration are necessary phenomena in situations such as fracture due to osteoporosis, cleft lip and palate (CLP) and surgery (for example, cardiac surgery, plastic surgery and cancer surgery). Osteoporosis is characterized by low bone mineral density, strength and micro-architectural deterioration, leading to an increased risk of fragility fractures [1]. With an increasing aging population, the number of osteoporosis fractures is expected to increase in the near future. CLP causes problems with feeding, speaking and hearing that can be corrected to varying degrees by surgery and dental treatment. The development of bone graft materials for treating CLP has been reported in a clinical study [3]. Many materials similar to bone have been used in surgery. In cardiac surgery, bone wax and sternal pins are used

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