Resveratrol facilitates bone marrow mesenchymal stem cells (BMSCs) differentiation to prevent osteoporosis via restraining of secreted frizzled-related protein 1 expression

2021 ◽  
Vol 11 (10) ◽  
pp. 1636-1644
Author(s):  
Zuozhong Liu ◽  
Chunling Shui ◽  
Lili Huang ◽  
Yiming Qu

Secreted frizzled-related protein 1 (SFRP1) is associated with cell differentiation, and its expression can be modulated by resveratrol. However, their impacts on bone marrow mesenchymal stem cells (BMSCs)-induced osteogenesis and ovariectomy-triggered bone loss remain unclear. Therefore, we in this study aimed to dissect the regulation of resveratrol on SFRP1, along with its sequential effects on differentiation and osteoporosis prevention of BMSCs. The SFRP1 expression in the ovariectomized (OVX) mice-originated bone tissues, BMSCs and bone marrow-derived macrophages (BMMs), during their differentiation towards osteoblasts and chondrocytes, was quantified by qRT-PCR and Western-blot. SFRP1-siRNA was applied for studying its influence on osteogenesis of BMSCs. Additionally, we evaluated the impacts of resveratrol on OVX mice and SFRP1 expression. SFRP1 was significantly up-regulated in the OVX mice-derived bone tissues and BMSCs, but gradually decreased during osteogenesis. Its expression was not significantly changed in BMSCs during their differentiation towards osteoclasts or in BMMs. The knockout of SFRP1 significantly improved mineralization potentiality, alkaline phosphatase activity and expression of several osteoblast-specific genes. Moreover, the bone loss was ameliorated in OVX mice treated with resveratrol, whose therapeutic effects were achieved by facilitating the expression of osteogenesis-associated genes while suppressing the SFRP1 expression. We also observed that the SFRP1 exerted a negative effect on osteogenesis of BMSCs and estrogen deficiency-induced osteoporosis, enabling itself to be an indicator of osteogenesis and also a molecular target for PMOP treatment. Resveratrol is a suppressor of SFRP1that can be applied as an active ingredient for treating PMOP.

2021 ◽  
Vol 25 (19) ◽  
pp. 9281-9294
Author(s):  
Yi Jin ◽  
Min Xu ◽  
Hai Zhu ◽  
Chen Dong ◽  
Juan Ji ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5133-5133
Author(s):  
Jun Ren ◽  
Hanfang Jiang ◽  
Lijun Di ◽  
Guohong Song

Abstract Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC. Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well. Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice. Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Zhao ◽  
Zhiying He ◽  
Dandan Huang ◽  
Jun Gao ◽  
Yanfang Gong ◽  
...  

Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation.Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was also analyzed.Results. The survival rate of the transplantation group was significantly higher compared to the control group (p<0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p<0.05).Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Cao ◽  
Shike Hou ◽  
Hui Ding ◽  
Ziquan Liu ◽  
Meijuan Song ◽  
...  

Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs afterin vivoadministration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time.Ex vivoorgan imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs.


Author(s):  
Gang Xu ◽  
Zheng Ding ◽  
Hui-feng Shi

Abstract Background Bone marrow mesenchymal stem cells (BMMSCs) can be used for bone regeneration in the specified condition. Osteogenic differentiation of BMMSCs is controlled by microRNAs (miRNAs) and other factors. This study was aimed to identify the role and mechanism of miR-889 in regulating the osteogenic differentiation of BMMSCs. Methods Osteoporosis patients and normal control bone tissues were collected and used PCR techniques to identify the change of miR-889 and WNT7A. Moreover, the dynamic change of miR-889 and WNT7A during osteogenic differentiation of BMMSCs was also measured. Bioinformatic analysis was performed to identify the target genes and potential pathways of miR-889. Then, we constructed miR-889 mimic and inhibitor, ALP staining, ARS, osteoblastic-related protein, and Wnt β-catenin signaling pathway-related protein were also measured. WNT7A siRNA was also used to verify the function of miR-889. Results In the present study, we showed that miR-889 expression was upregulated in osteoporosis patients than healthy control. However, the miR-889 expression was downregulated during osteogenic differentiation. Bioinformatics analysis found that miR-889 targets 666 genes and mainly through Wnt β-catenin signaling pathway. Administrated miR-889 mimic, the ALP activity, and calcium deposition were decreased than the control group, while miR-889 inhibitor shown the opposite trend. And miR-889 could bind the 3′UTR of WNT7A. We further used WNT7A siRNA to explore the function of miR-889, and the results revealed that co-cultured with miR-889 inhibitor and WNT7A siRNA was associated with a reduction of ALP activity and calcium deposition and osteoblastic-related proteins than miR-889 inhibitor alone. Conclusion Our results revealed that miR-889 plays a negative role in inducing osteogenic differentiation of BMSCs through Wnt β-catenin signaling pathway.


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