Teriparatide Promotes Bone Marrow Mesenchymal Stem Cell Proliferation and Differentiation by Down-Regulating miR-339 to Target DLX5

2019 ◽  
Vol 9 (6) ◽  
pp. 816-821
Author(s):  
Jiankun Liu ◽  
Qiangsong Wang ◽  
Guiming Sun ◽  
Qiang Yang

Osteoporosis (OP) is a metabolic bone disease which is characterized as loss of bone mineral content, decreased bone density, bone microstructural destruction, and reduced bone biomechanical evaluation index. Proliferation and differentiation of bone marrow mesenchymal stem cells (MSCs) is important for the treatment of OP. It is proposed that down-regulation of miR-339 can target DLX to promote the proliferation and differentiation of MSCs. However, whether teriparatide promotes osteogenic differentiation through this pathway remains unclear. MSCs were isolated from 4–6 week-old Wister rats. The effect of teriparatide on cell proliferation was evaluated by tetrazolium salt colorimetric method (MTT) and BrdU staining. Cell differentiation was measured by alkaline phosphatase staining. miR-339 expression was detected by real-time quantitative PCR (qRT-PCR). DLX5 expression was detected by Western-blot. It was found that teriparatide can promote the proliferation and differentiation of MSCs. MiR-339 level was significantly decreased and DLX5 expression was significantly upregulated after teriparatide treatment. After knocking down miR-339, teriparatide-induced upregulation of DLX5 by was attenuated. Teriparatide promotes the proliferation and differentiation of MSCs by down-regulating miR-339 to improve osteoporosis. It provides theoretical and experimental basis for the treatment of osteoporosis by teriparatide.

2010 ◽  
Vol 107 (7) ◽  
pp. 913-922 ◽  
Author(s):  
Konstantinos E. Hatzistergos ◽  
Henry Quevedo ◽  
Behzad N. Oskouei ◽  
Qinghua Hu ◽  
Gary S. Feigenbaum ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanxiu Sun ◽  
Yu Yuan ◽  
Wei Wu ◽  
Le Lei ◽  
Lingli Zhang

AbstractBone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.


2022 ◽  
Vol 12 (2) ◽  
pp. 273-278
Author(s):  
Daqing Jiang ◽  
Xianxin Xie ◽  
Cong Wang ◽  
Weijie Li ◽  
Jianjun He

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.


2021 ◽  
Author(s):  
Yu Zhou ◽  
Chaozong Liu ◽  
Zhenwei Zhou ◽  
Xin Li ◽  
Songchuan Su ◽  
...  

Abstract Background: The development of Chinese medicine has been practised in China over a long period of time, and China has long used single medicines in various forms of decoction to treat illnesses, and later learned to combine several medicines to form formulas to enhance the effects of the medicines. The use of Chinese herbal medicines and formulas has played a pivotal role in the prevention and treatment of diseases in China since ancient times. The application of Chinese herbal preparations in the field of osteoporosis treatment has received widespread attention, and Gujin Dan(GJD) is one of the representative herbal formulas, however, the exact minute mechanism of its treatment of osteoporosis remains to be elucidated.Methods: In the study, we prepared an aqueous extract of GJD and measured the effect of different administration concentrations of GJD on cell proliferation by CCK-8 assay, and the effect of GJD on cell differentiation ability by Alizarin Red S Staining, Alkaline Phosphatase Staining and quantitative assay. Changes in gene expression patterns of MC3T3-E1 cells under GJD treatment were investigated by RNA-seq analysis and validation methods.Results: We demonstrate that GJD promotes the proliferation and differentiation of Mc3t3-e1 cells through the regulation of multiple functional genes. This was mainly achieved by regulating the expression levels of four categories of genes that promote the proliferation of Mc3t3-e1 cells or osteoblasts, inhibit apoptosis and autophagy, inhibit osteoclast formation and differentiation, and promote osteoblast differentiation. In addition, GJD slightly increased the expression levels of gene markers in osteoblasts. Conclusions: Our findings suggest that GJD promotes proliferation and differentiation of MC3T3-E1 cells and inhibits osteoclastogenesis and differentiation, as well as apoptosis and autophagy, through the synergistic interaction of various herbs and their active components in GJD. This study has significantly improved the current understanding of the molecular effects of GJD on MC3T3-E1 cells. This study also provides new ideas for possible strategies to further prevent and treat bone metabolism-related diseases using traditional Chinese medicinal preparations.


2022 ◽  
Vol 12 (4) ◽  
pp. 854-861
Author(s):  
Jing Li ◽  
Bo Xie ◽  
Hu Wang ◽  
Chengsong Chen ◽  
Chengwu Pan ◽  
...  

Certain progress has been made in the therapeutic method against gastric cancer such as surgical operation combined with chemotherapy and radiation therapy in recent years. But the therapeutic efficacy and prognosis on gastric cancer was still not satisfactory. The function of exosome of miR-328–3p secreted by bone marrow stromal cells (BMSCs) on restraining the gastric cancer was studied in the present study. The BMSCs with highly-expressed miR-328-3p was established. The exosome in cell supernatant was collected. The exosome of BMSCs and MSCs with highlyexpressed miR-328-3p was added into SGC-7901 cells followed by analysis of miR-328-3p level by Real-time PCR and TFF3 (Trefoil Factor 3) level in exosome by Western blot, cell proliferation, expression of E-cadherin, Vimentin and Caspase-3. miR-328-39 expression was reduced and TFF3 was elevated in gastric cancer tissue (P < 0.05). miR-328-3p was upregulated and TFF3 was downregulated after addition of BMSCs exosomes along with increased cell proliferation and reduced E-cadherin and Caspase3 expression (P < 0.05). In conclusion, exosome of BMSCs could be regulated by miR-328-3p and TFF3 expression is restrained so as to regulate the biological behaviors of gastric cancer cell.


2021 ◽  
pp. 1-13
Author(s):  
Yuying Wang ◽  
Rui He ◽  
Anqi Yang ◽  
Rui Guo ◽  
Jie Liu ◽  
...  

BACKGROUND: The effectiveness and availability of conservative therapies for osteonecrosis of the femoral head (ONFH) are limited. Transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with Bio-Oss, which is a good bone scaffold biomaterial for cell proliferation and differentiation, is a new potential therapy. Of note, the expression of miRNAs was significantly modified in cells cultured with Bio-Oss, and MiR-214 was correlated positively with osteonecrosis. Furthermore, miR-214 was upregulated in cells exposed to Bio-Oss. OBJECTIVE: To investigate whether targeting miR-214 further improves the transplantation effect. METHODS: We treated BMSCs with agomiR-214 (a miR-214 agonist), antagomiR-214 (a miR-214 inhibitor), or vehicle, followed by their transplantation into ONFH model rats. RESULTS: Histological and histomorphometric data showed that bone formation was significantly increased in the experimental groups (Bio-Oss and BMSCs treated with antagomiR-214) compared with other groups. CONCLUSIONS: miR-214 participates in the inhibition of osteoblastic bone formation, and the inhibition of miR-214 to bone formation during transplantation therapy with Bio-Oss combined with BMSCs for ONFH.


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