Aluminum trichloride inhibits osteoblastic differentiation through inactivation of Wnt/β-catenin signaling pathway in rat osteoblasts

2016 ◽  
Vol 42 ◽  
pp. 198-204 ◽  
Author(s):  
Zheng Cao ◽  
Yang Fu ◽  
Xudong Sun ◽  
Qiuyue Zhang ◽  
Feibo Xu ◽  
...  
2018 ◽  
Vol 01 (01) ◽  
pp. 33-41
Author(s):  
Qin Bian ◽  
Shufen Liu ◽  
Yongjian Zhao ◽  
Jianhua Huang ◽  
Ziyin Shen

Objective: Icariin (ICA), an extract from epimedium, has been reported to be effective in promoting bone formation. The objective of the study is to search for the molecular targets of ICA in bone mesenchymal stem cells (bMSCs) from the mice with ovariectomy (OVX)-induced osteoporosis. Methods: Six-month-old Imprinting Control Region (ICR) mice that underwent OVX were treated with ICA. After three months, bone mass was evaluated by microcomputed tomography, morphometry and immunohistological detection. bMSCs were isolated from the femur and tibia to observe the self-renewal and differentiation capacities using colony-forming unit fibroblastic (CFU-F), colony-forming unit adipocyte (CFU-Adipo) and alkaline phosphatase (ALP) staining. In addition, microarray of bMSCs ex vivo was measured two weeks after ICA treatment and analyzed by heatmap and pathway analysis. The signaling pathway was further explored by western blot assay and inhibitors of p38 and ERK: SB203508 and PD98059. Results: [Formula: see text]CT displayed a decrease in bone mass for three months after OVX. ICA treatment increased the trabecular thickness (Tb.Th), osteoblast number while decreased osteoclast number, elevating osteocalcin (OC) protein levels in vivo and facilitating the self-renewal and osteoblastic differentiation of bMSCs ex vivo. Microarray data indicated ICA rescued several gene expressions that were dysregulated by OVX. Pathway analysis revealed that the core genes acted by ICA were highly involved in MAPK signaling pathway. Further study demonstrated ICA suppressed ERK while stimulated p38 phosphorylation to promote osteoblastic differentiation in vitro. Conclusion: ICA promotes osteoblastic differentiation of bMSCs in OVX mice. MAPK signaling pathway might be involved in the process.


2019 ◽  
Vol 44 (2) ◽  
pp. 402-411 ◽  
Author(s):  
Guiling Zhu ◽  
Bin Ma ◽  
Penghong Dong ◽  
Junjun Shang ◽  
Xiaochuan Gu ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yue Sun ◽  
Yuzhen Liang ◽  
Zhengming Li ◽  
Ning Xia

Liraglutide is a glucagon-like peptide-1 analogue widely used in the treatment of type 2 diabetes mellitus. However, the effects of liraglutide on osteoblast proliferation and differentiation in MC3T3-E1 cells have not been fully elucidated. In the present study, the promoting effects of liraglutide were investigated in MC3T3-E1 cells. The results indicated that cell viability was affected following the treatment of the cells with different concentrations of liraglutide (0, 10, 100, and 1000 nM) at different time periods of culture (24, 48, and 72 h). Moreover, the activity levels of alkaline phosphatase and the number of mineralized nodules in MC3T3-E1 cells were significantly increased following treatment with 100 nM liraglutide. The mRNA and protein levels of Col-1, OPG, and OCN in MC3T3-E1 cells were also markedly increased following 100 nM liraglutide treatment compared with those of the control group. The expression levels of the ERK5 signaling pathway key proteins (MEK5, p-ERK5, ERK5, and NUR77) were increased following liraglutide treatment in MC3T3-E1 cells, and the gene expression levels of the ERK5 signaling pathway were also elevated. Moreover, the ERK5 inhibitor XMD8-92 significantly decreased the expression levels of p-ERK5 and NUR77 as well as the proliferation of osteoblasts. However, these changes could be rescued by liraglutide to some extent. Therefore, these results revealed that liraglutide may promote osteoblastic differentiation and proliferation in MC3T3-E1 cells via the activation of the ERK5 signaling pathway.


2012 ◽  
Vol 8 (10) ◽  
pp. 1310-1322 ◽  
Author(s):  
Weizhuo Wang ◽  
Douglas Olson ◽  
Gang Liang ◽  
Renny T Franceschi ◽  
Chunyi Li ◽  
...  

Chemosphere ◽  
2018 ◽  
Vol 203 ◽  
pp. 170-178 ◽  
Author(s):  
Haiyang Zhang ◽  
Peiyan Wang ◽  
Hongyan Yu ◽  
Kaiyuan Yu ◽  
Zheng Cao ◽  
...  

2020 ◽  
Author(s):  
Nan Chen ◽  
Hao Yang ◽  
Lijun Song ◽  
Hua Li ◽  
Yi Liu ◽  
...  

Osteogenic differentiation is an important process of new bone formation, miR-409-3p has been reported to be upregulated in osteogenic differentiation of human bone marrow mesenchymal stem cells (MSCs). To investigate the regulatory effect of miR-409-3p on osteogenic differentiation of MSCs and its molecular mechanism, the expression of miR-409-3p in osteoblast (HCO) and bone marrow-derived MSCs (MSC-A, MSC-B, MSC-U) were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The binding of miR-409-3p to SCAI in MSC-B was investigated by dual-luciferase reporter gene assay. MSC-B were selected to transfect with miR-409-3p analog/complementary sequence (cs), miR-409-3p analog + SCAI and miR-409-3p cs + small interfering (si)-SCAI, as well as control, respectively. The alkaline phosphatase activity, alizarin red staining, and the expression of osteogenic markers in MSC-B during osteoblastic differentiation were tested by RT-qPCR and Western blotting, respectively. The Wnt/β-catenin pathway was inhibited by dickkopf-related protein 1 to get the roles of miR-409-3p during the osteoblastic differentiation of MSC-B when transfected with miR-409-3p analog. The expression of miR-409-3p in HCO was higher than that in these three MSCs, showing an increasing time-dependent trend on the 0 and 21th day of osteoblastic differentiation. MiR-409-3p directly regulated SCAI by targeting SCAI 3′UTR. Further, miR-409-3p suppressed SCAI expression, but SCAI upregulation suppressed the osteoblastic differentiation, as well as reduced the relative mRNA/protein expression of Wnt/β-catenin signaling pathway-related genes. Importantly, disruption of Wnt signaling also blocked miR-409-3p induced osteoblastic differentiation of MSCs. Therefore, miR-409-3p promotes osteoblastic differentiation through the activation of the Wnt/β-catenin pathway by downregulating SCAI expression.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Zhao ◽  
Gengyan Xing ◽  
Aiyuan Wang

Abstract Background This study was conducted with the aim of exploring the effect of the BMP signaling pathway on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (rBMSCs) in rats with osteoporosis (OP). Methods The bilateral ovaries of female SD rats were resected for the establishment of a rat OP model. The osteoblastic differentiation of isolated rBMSCs was identified through osteogenic induction. Adipogenetic induction and flow cytometry (FCM) were used to detect adipogenic differentiation and the expression of rBMSC surface markers. The rBMSCs were grouped into the blank group, NC group, si-BMP2 group, and oe-BMP2 group. The expression levels of key factors and osteogenesis-related factors were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The formation of calcified nodules was observed by alizarin red staining. ALP activity was measured by alkaline phosphatase staining. Results The rats with OP had greater weight but decreased bone mineral density (BMD) than normal rats (all P < 0.01). The rBMSCs from rats with OP were capable of osteoblastic differentiation and adipogenic differentiation and showed high expression of CD44 (91.3 ± 2.9%) and CD105 (94.8 ± 2.1%). Compared with the blank group, the oe-BMP2 group had elevated BMP-2 and Smad1 levels and an increase in calcified nodules and ALP-positive staining areas (all P < 0.05). Moreover, the expression levels of Runx2, OC, and OPN in the oe-BMP2 group were relatively higher than those in the blank group (all P < 0.05). The findings in the si-BMP2 group were opposite to those in the oe-BMP2 group. Conclusion BMP signaling pathways activated by BMP-2 can promote the osteoblastic differentiation of rBMSCs from rats with OP.


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