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Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation from multipotent bone marrow stromal cells and bone formation.

ABSTRACT: Strategies for efficient osteogenic differentiation and bone formation from stem cells would have clinical applications in treating nonunion fracture healing. Many researchers have attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. Therefore, development of specific stimulators of bone formation has therapeutic significance in the treatment of osteoporosis. To date, investigations of the mature forms of bone morphogenetic proteins (BMPs) have focused on regulation of bone generation. However, we previously identified new peptides from the immature precursor of BMP, and further analysis of these proteins should be performed. In this study, we identified a new peptide called bone-forming peptide-2 (BFP-2), which has stronger osteogenic differentiation-promoting activity than BMP-7. BFP-2 treatment of multipotent bone marrow stromal cells (BMSCs) induced expression of active alkaline phosphatase. In addition, BFP-2 enhanced CD44 and CD51 expression levels and increased Ca²⁺ content in BMSCs. Moreover, radiography at 8 weeks revealed that animals that had received transplants of BFP-2-treated BMSCs showed substantially increased bone formation compared with animals that had received BMSCs treated with BMP-7. Our findings indicate that BFP-2 may be useful in the development of adjuvant therapies for bone-related diseases.

SUBMITTER: Kim HK

PROVIDER: S-EPMC5454442 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation from multipotent bone marrow stromal cells and bone formation.

Kim Hyung Keun HK Lee Jun Sik JS Kim Ji Hyun JH Seon Jong Keun JK Park Kyung Soon KS Jeong Myung Ho MH Yoon Taek Rim TR

Experimental & molecular medicine 20170512 5

Strategies for efficient osteogenic differentiation and bone formation from stem cells would have clinical applications in treating nonunion fracture healing. Many researchers have attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. Therefore, development of specific stimulators of bone formation has therapeutic significance in the treatment of osteoporosis. To date, investigations of the mature forms of bone morphogeneti ...[more]

PMID: 28496198

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Project description:The authors' previous study demonstrated that miR‑128 may exert an inhibitory effect on the osteogenic differentiation of bone marrow‑derived mesenchymal stem cells (BM‑MSCs), but its downstream mechanisms remain to be elucidated. The aim of the present study was to investigate the microRNA (miRNA/miR) and mRNA profiles of differentiated and undifferentiated BM‑MSCs and explore new downstream targets for miR‑128. The sequencing datasets of GSE107279 (miRNA) and GSE112318 (mRNA) were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) and genes (DEGs) were identified using the DESeq2 method. The target genes of DEMs were predicted by the miRwalk 2.0 database. The hub target genes of miR‑128 were screened by constructing the protein‑protein interaction (PPI) network and module analysis. The expression levels of miR‑128 and crucial target genes were validated by reverse transcription‑quantitative (RT‑q) PCR before or after transfection of miR‑128 mimics to BM‑MSCs. The miRNA expression profile analysis identified miR‑128 as one of the significantly downregulated DEMs (total 338) in differentiated BM‑MSCs compared with the undifferentiated control. A total of 103 predicted target genes of miR‑128‑3p were overlapped with upregulated DEGs. By calculating the topological properties of each protein in the PPI network, 6 upregulated genes (KIT, NTRK2, YWHAB, GAB1, AXIN1 and RUNX1; fold change was the highest for NTRK2) were considered to be hub genes. Of these, 4 were enriched in module 4 (RUNX1, KIT, GAB1 and AXIN1; RUNX1 was particularly crucial as it can interact with the others), while one was enriched in module 7 (YWHAB). The expression levels of miR‑128 and these 6 target genes during the osteogenic differentiation were experimentally confirmed by RT‑qPCR. In addition, the expression levels of these 6 genes were significantly reversed after transfection of miR‑128‑3p mimics into rat BM‑MSCs compared with the miR‑control group. These findings indicated that miR‑128‑3p may inhibit the osteoblast differentiation of BM‑MSCs by downregulation of these 6 genes, particularly RUNX1, YWHAB and NTRK2.

Dataset Information

Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation from multipotent bone marrow stromal cells and bone formation.

Publications

Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation from multipotent bone marrow stromal cells and bone formation.

Similar Datasets

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