Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Promote Osteoporosis and Osteoblast Proliferation by Inhibiting Bax/Bcl-2/Caspase Signaling Pathway

2020 ◽  
Vol 10 (3) ◽  
pp. 418-423
Author(s):  
Shengxing Liu ◽  
Kaizhong Zhu ◽  
Hao Qi ◽  
Hai Zhao ◽  
Dingzhong Chen

The current treatment for osteoporosis cannot restore the lost bone mass. Exosomes can not only delay bone loss, but also promote osteogenic proliferation and differentiation. This study aims to determine whether BMSCs-derived exosomes could improve osteoporosis in rats. A rat model of osteoporosis was established by excising bilateral ovaries. Whole bone marrow cell inoculation method and adherent purification were used to culture rat bone marrow mesenchymal stem cells (BMSCs). Osteoporosis rats were treated with BMSCs-derived exosomes followed by analysis of serum osteocalcin level by ELISA and bone mineral density and volume fraction by Micro-CT. Osteoblasts were treated with exosomes followed by analysis of cell proliferation by CCK-8 assay and expression of key molecules in the apoptotic signaling by real-time PCR and Western blot. Serum osteocalcin, bone mineral density and volume fraction in OVX group were significantly lower than those in control group and Exo group (P < 0.05) with significant differences between Exo group and CON group. With the increase of exosome concentration, the survival rate of osteoblasts was increased gradually. Cleaved Caspase-3 expression was reduced and Bcl-2 level was elevated gradually. BMSCs-derived exosomes can promote osteoblast proliferation by inhibiting apoptotic signaling pathway and improving osteoporosis.

2020 ◽  
Vol 10 (12) ◽  
pp. 1865-1870
Author(s):  
Yang Ying ◽  
Binghao Zhao ◽  
Wei Qian ◽  
Li Xu

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential with multi-directional differentiation. Progranulin prevents bone degradation, inhibits inflammation and protects bone tissue. However, the role of Progranulin in osteoporotic BMSCs is unclear. Osteoporosis (OP) rat models were prepared by ovarian removal and treated with different doses (5 and 10 μM) of Progranulin followed by analysis of BMP-2 level by ELISA, bone mineral density and ALP activity. OP rat BMSCs were isolated and assigned into control group and Progranulin group followed by analysis of Progranulin level by ELISA, cell proliferation by MTT assay, RUNX2 and COL1A1 mRNA level by Real time PCR, and PI3K/Akt/PPARγ signaling protein level by Western blot. Progranulin treatment of OP rats dose-dependently increased BMP-2 expression, bone density and ALP activity. Compared with OP group, there were significant differences (P <0.05). Progranulin expression and BMSCs proliferation was increased, and RUNX2 and COL1A1 mRNA expression was elevated in Progranulin-treated OP group along with increased PI3K/Akt expression and decreased PPARγ protein expression. Compared with OP group, the difference was statistically significant, and the change was more significant with increasing concentration (P <0.05). Progranulin promotes BMSCs osteogenic differentiation and proliferation by regulating PI3K/Akt/PPARγ signaling pathway, which is beneficial for OP rats’ bone synthesis.


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