PUBLICATION
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
- Authors
- Shin, M.K., Jang, Y.H., Yoo, H.J., Kang, D.W., Park, M.H., Kim, M.K., Seo, D.S., Kim, S.D., Min, G., Rhyu, H.K., Bae, Y.S., and Min, D.S.
- ID
- ZDB-PUB-110317-25
- Date
- 2011
- Source
- The Journal of biological chemistry 286(19): 17133-43 (Journal)
- Registered Authors
- Keywords
- Adipocyte, Cell differentiation, ERK, Signal transduction, Stem cell
- MeSH Terms
-
- Adipocytes/cytology
- Animals
- Bone Marrow Cells/cytology*
- Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
- Cell Differentiation
- Cyclosporine/pharmacology
- Humans
- Mesenchymal Stem Cells/cytology*
- N-Formylmethionine Leucyl-Phenylalanine/pharmacology*
- Osteoblasts/cytology*
- PPAR gamma/metabolism
- Phospholipase D/metabolism
- Rabbits
- Receptors, Formyl Peptide/chemistry
- Receptors, Formyl Peptide/physiology*
- Signal Transduction
- Type C Phospholipases/metabolism
- PubMed
- 21372136 Full text @ J. Biol. Chem.
Citation
Shin, M.K., Jang, Y.H., Yoo, H.J., Kang, D.W., Park, M.H., Kim, M.K., Seo, D.S., Kim, S.D., Min, G., Rhyu, H.K., Bae, Y.S., and Min, D.S. (2011) 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. The Journal of biological chemistry. 286(19):17133-43.
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 (MSCs) is unknown. In the current study, we attempted to determine whether fMLP regulates differentiation of MSCs derived from bone marrow. Analysis by q-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 PPARg1, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping