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

Bone
Basem M AbdallahMoustapha Kassem

Abstract

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 thr...Continue Reading

Citations

Apr 16, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Fuhua YangShingo Oda
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Basem M Abdallah, Enas M Ali
Jun 14, 2019·Frontiers in Endocrinology·Alessandro CorsiOlaia Naveiras
Jan 2, 2021·Frontiers in Cell and Developmental Biology·Qian LiuGuangwei Wang
Feb 13, 2021·Trends in Biochemical Sciences·Sandeep Satapathy, Mark R Wilson
Feb 16, 2021·Archives of Biochemistry and Biophysics·Da LiuMin Qiu
Apr 17, 2021·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Basem M Abdallah
Jul 3, 2021·International Journal of Molecular Sciences·José V ÁlvarezMaría L Couce

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