N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP) promotes osteoblast differentiation via the N-formyl peptide receptor 1-mediated signaling pathway in human mesenchymal stem cells from bone marrow

Min Kyoung Shin, Young Hoon Jang, Hyun Jung Yoo, Dong Woo Kang, Mi Hee Park, Mi Kyoung Kim, Ju Hyun Song, Sang Doo Kim, Gyesik Min, Hyung Keun You, Kang Yell Choi, Yoe Sik Bae, Do Sik Min

Research output: Contribution to journalArticle

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Abstract

Binding of N-formyl-methionyl-leucyl-phenylalanine (fMLP) to its specific cell surface receptor, N-formyl peptide receptor (FPR), triggers different cascades of biochemical events, eventually leading to cellular activation. However, the physiological role of fMLP and FPR during differentiation of mesenchymal stem cells is unknown. In this study, we attempted to determine whether fMLP regulates differentiation of mesenchymal stem cells derived from bone marrow. Analysis by quantitative-PCR and flow cytometry showed significantly increased expression of FPR1, but not FPR2 and FPR3, during osteoblastic differentiation. fMLP, a specific ligand of FPR1, promotes osteoblastic commitment and suppresses adipogenic commitment under differentiation conditions. Remarkably, fMLP-stimulated osteogenesis is associated with increased expression of osteogenic markers and mineralization, which were blocked by cyclosporine H, a selective FPR1 antagonist. In addition, fMLP inhibited expression of peroxisome proliferator-activated receptor-γ1, a major regulator of adipocytic differentiation. fMLP-stimulated osteogenic differentiation was mediated via FPR1-phospholipase C/phospholipase D-Ca2+-calmodulin-dependent kinase II-ERK-CREB signaling pathways. Finally, fMLP promoted bone formation in zebrafish and rabbits, suggesting its physiological relevance in vivo. Collectively, our findings provide novel insight into the functional role of fMLP in bone biology, with important implications for its potential use as a therapeutic agent for treatment of bone-related disorders.

Original languageEnglish
Pages (from-to)17133-17143
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number19
DOIs
Publication statusPublished - 2011 May 13

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Formyl Peptide Receptor
N-Formylmethionine Leucyl-Phenylalanine
Osteoblasts
Stem cells
Mesenchymal Stromal Cells
Bone
Bone Marrow
Osteogenesis
Bone and Bones
Phospholipase D
Calcium-Calmodulin-Dependent Protein Kinases
Peroxisome Proliferator-Activated Receptors
Flow cytometry
Cell Surface Receptors
Type C Phospholipases
Zebrafish
Calmodulin
Flow Cytometry
Phosphotransferases
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Shin, Min Kyoung ; Jang, Young Hoon ; Yoo, Hyun Jung ; Kang, Dong Woo ; Park, Mi Hee ; Kim, Mi Kyoung ; Song, Ju Hyun ; Kim, Sang Doo ; Min, Gyesik ; You, Hyung Keun ; Choi, Kang Yell ; Bae, Yoe Sik ; Min, Do Sik. / N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP) promotes osteoblast differentiation via the N-formyl peptide receptor 1-mediated signaling pathway in human mesenchymal stem cells from bone marrow. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 19. pp. 17133-17143.
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abstract = "Binding of N-formyl-methionyl-leucyl-phenylalanine (fMLP) to its specific cell surface receptor, N-formyl peptide receptor (FPR), triggers different cascades of biochemical events, eventually leading to cellular activation. However, the physiological role of fMLP and FPR during differentiation of mesenchymal stem cells is unknown. In this study, we attempted to determine whether fMLP regulates differentiation of mesenchymal stem cells derived from bone marrow. Analysis by quantitative-PCR and flow cytometry showed significantly increased expression of FPR1, but not FPR2 and FPR3, during osteoblastic differentiation. fMLP, a specific ligand of FPR1, promotes osteoblastic commitment and suppresses adipogenic commitment under differentiation conditions. Remarkably, fMLP-stimulated osteogenesis is associated with increased expression of osteogenic markers and mineralization, which were blocked by cyclosporine H, a selective FPR1 antagonist. In addition, fMLP inhibited expression of peroxisome proliferator-activated receptor-γ1, a major regulator of adipocytic differentiation. fMLP-stimulated osteogenic differentiation was mediated via FPR1-phospholipase C/phospholipase D-Ca2+-calmodulin-dependent kinase II-ERK-CREB signaling pathways. Finally, fMLP promoted bone formation in zebrafish and rabbits, suggesting its physiological relevance in vivo. Collectively, our findings provide novel insight into the functional role of fMLP in bone biology, with important implications for its potential use as a therapeutic agent for treatment of bone-related disorders.",
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N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP) promotes osteoblast differentiation via the N-formyl peptide receptor 1-mediated signaling pathway in human mesenchymal stem cells from bone marrow. / Shin, Min Kyoung; Jang, Young Hoon; Yoo, Hyun Jung; Kang, Dong Woo; Park, Mi Hee; Kim, Mi Kyoung; Song, Ju Hyun; Kim, Sang Doo; Min, Gyesik; You, Hyung Keun; Choi, Kang Yell; Bae, Yoe Sik; Min, Do Sik.

In: Journal of Biological Chemistry, Vol. 286, No. 19, 13.05.2011, p. 17133-17143.

Research output: Contribution to journalArticle

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T1 - N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP) promotes osteoblast differentiation via the N-formyl peptide receptor 1-mediated signaling pathway in human mesenchymal stem cells from bone marrow

AU - Shin, Min Kyoung

AU - Jang, Young Hoon

AU - Yoo, Hyun Jung

AU - Kang, Dong Woo

AU - Park, Mi Hee

AU - Kim, Mi Kyoung

AU - Song, Ju Hyun

AU - Kim, Sang Doo

AU - Min, Gyesik

AU - You, Hyung Keun

AU - Choi, Kang Yell

AU - Bae, Yoe Sik

AU - Min, Do Sik

PY - 2011/5/13

Y1 - 2011/5/13

N2 - Binding of N-formyl-methionyl-leucyl-phenylalanine (fMLP) to its specific cell surface receptor, N-formyl peptide receptor (FPR), triggers different cascades of biochemical events, eventually leading to cellular activation. However, the physiological role of fMLP and FPR during differentiation of mesenchymal stem cells is unknown. In this study, we attempted to determine whether fMLP regulates differentiation of mesenchymal stem cells derived from bone marrow. Analysis by quantitative-PCR and flow cytometry showed significantly increased expression of FPR1, but not FPR2 and FPR3, during osteoblastic differentiation. fMLP, a specific ligand of FPR1, promotes osteoblastic commitment and suppresses adipogenic commitment under differentiation conditions. Remarkably, fMLP-stimulated osteogenesis is associated with increased expression of osteogenic markers and mineralization, which were blocked by cyclosporine H, a selective FPR1 antagonist. In addition, fMLP inhibited expression of peroxisome proliferator-activated receptor-γ1, a major regulator of adipocytic differentiation. fMLP-stimulated osteogenic differentiation was mediated via FPR1-phospholipase C/phospholipase D-Ca2+-calmodulin-dependent kinase II-ERK-CREB signaling pathways. Finally, fMLP promoted bone formation in zebrafish and rabbits, suggesting its physiological relevance in vivo. Collectively, our findings provide novel insight into the functional role of fMLP in bone biology, with important implications for its potential use as a therapeutic agent for treatment of bone-related disorders.

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