Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1/2 signaling pathway

Autor: Moustapha Kassem, Abdullah M. Alzahrani, Basem M. Abdallah
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Physiology
sCLU
Endocrinology
Diabetes and Metabolism
Cellular differentiation
MAP Kinase Signaling System/physiology
Computational biology
Mice
0302 clinical medicine
Predictive toxicology
Adipocytes
Cells
Cultured
Adipocyte
Osteoblast differentiation
biology
Adipocytes/cytology
Chemistry
Osteoblast
Cell Differentiation
Cell biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
BMSCs
Signal transduction
Stem cell
Systems biology
Signal Transduction
Histology
Stromal cell
MAP Kinase Signaling System
Blotting
Western
Enzyme-Linked Immunosorbent Assay
03 medical and health sciences
medicine
Cell Differentiation/physiology
Animals
Clusterin/metabolism
Osteoblasts
Clusterin
Signal Transduction/physiology
Cell growth
Mesenchymal Stem Cells/cytology
Mesenchymal stem cell
Osteoblasts/cytology
Mesenchymal Stem Cells
Alkaline Phosphatase
Pesticide
Mice
Inbred C57BL
030104 developmental biology
Pyriproxyfen
Toxicity testing
biology.protein
Mesenchymal stem cells
Developmental neurotoxicity
Alkaline Phosphatase/genetics
Zdroj: Abdallah, B, Alzahrani, A M & Kassem, M 2018, ' Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1/2 signaling pathway ', Bone, vol. 110, pp. 221-229 . https://doi.org/10.1016/j.bone.2018.02.018
ISSN: 8756-3282
DOI: 10.1016/j.bone.2018.02.018
Popis: Secreted Clusterin (sCLU, also known as Apolipoprotein J) is an anti-apoptotic glycoprotein involved in the regulation of cell proliferation, lipid transport, extracellular tissue remodeling and apoptosis. sCLU is expressed and secreted by mouse bone marrow-derived skeletal (stromal or mesenchymal) stem cells (mBMSCs), but its functional role in MSC biology is not known. In this study, we demonstrated that Clusterin mRNA expression and protein secretion in conditioned medium increased during adipocyte differentiation and decreased during osteoblast differentiation of mBMSCs. Treatment of mBMSC cultures with recombinant sCLU protein increased cell proliferation and exerted an inhibitory effect on the osteoblast differentiation while stimulated adipocyte differentiation in a dose-dependent manner. siRNA-mediated silencing of Clu expression in mBMSCs reduced adipocyte differentiation and stimulated osteoblast differentiation of mBMSCs. Furthermore, the inhibitory effect of sCLU on the osteoblast differentiation of mBMSCs was mediated by the suppression of extracellular signal-regulated kinase (ERK1/2) phosphorylation. In conclusion, we identified sCLU as a regulator of mBMSCs lineage commitment to osteoblasts versus adipocytes through a mechanism mediated by ERK1/2 signaling. Inhibiting sCLU is a possible therapeutic approach for enhancing osteoblast differentiation and consequently bone formation.
Databáze: OpenAIRE
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