scholarly journals PARK7 promotes repair in early steroid-induced osteonecrosis of the femoral head by enhancing resistance to stress-induced apoptosis in bone marrow mesenchymal stem cells via regulation of the Nrf2 signaling pathway

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Fei Zhang ◽  
Yanglin Yan ◽  
Wuxun Peng ◽  
Lei Wang ◽  
Tao Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Femoral Head ◽  
Early Stage ◽  
Necrotic Area ◽  
Nrf2 Signaling Pathway ◽  
Marrow Mesenchymal Stem Cells ◽  
Resistance To Stress ◽  
Induced Apoptosis

AbstractNovel therapies for the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH) are urgently needed in orthopedics. Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides new strategies for treating this condition at the early stage. However, stress-induced apoptosis of BMSCs transplanted into the femoral head necrotic area limits the efficacy of BMSC transplantation. Inhibiting BMSC apoptosis is key to improving the efficacy of this procedure. In our previous studies, we confirmed that Parkinson disease protein 7 (PARK7) is active in antioxidant defense and can clear reactive oxygen species (ROS), protect the mitochondria, and impart resistance to stress-induced apoptosis in BMSCs. In this study, we investigated the mechanism driving this PARK7-mediated resistance to apoptosis in BMSCs. Our results indicate that PARK7 promoted the disintegration of nuclear factor (erythroid-derived 2)–like 2 (Nrf2)/Kelch-like echinacoside–associated protein 1 (Keap1) complex. The free Nrf2 then entered the nucleus and activated the genetic expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), and other antioxidant enzymes that clear excessive ROS, thereby protecting BMSCs from stress-induced apoptosis. To further explore whether PARK7-mediated resistance to stress-induced apoptosis could improve the efficacy of BMSC transplantation in early-stage SONFH, we transplanted BMSCs-overexpressing PARK7 into rats with early-stage SONFH. We then evaluated the survival of transplanted BMSCs and bone regeneration in the femoral head necrotic area of these rats. The results indicated that PARK7 promoted the survival of BMSCs in the osteonecrotic area and improved the transplantation efficacy of BMSCs on early-stage SONFH. This study provides new ideas and methods for resisting the stress-induced apoptosis of BMSCs and improving the transplantation effect of BMSCs on early-stage SONFH.

scholarly journals Lnc Tmem235 promotes repair of early steroid-induced osteonecrosis of the femoral head by regulating miR-34a-3p/BIRC5 to inhibit hypoxia-induced apoptosis of bone-marrow mesenchymal stem cells

2021 ◽  
Author(s):  
Fei Zhang ◽  
Wuxun Peng ◽  
Tao Wang ◽  
Jian Zhang ◽  
Wentao Dong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Femoral Head ◽  
Transmembrane Protein ◽  
B Cell Lymphoma ◽  
Competitive Binding ◽  
Regulated Expression ◽  
Marrow Mesenchymal Stem Cells ◽  
Induced Apoptosis

Abstract Bone-marrow mesenchymal stem cells (BMSCs) have been used in the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH). However, the hypoxic microenvironment in the osteonecrotic area leads to hypoxia-induced apoptosis of transplanted BMSCs, which limits their efficacy. Therefore, approaches that inhibit hypoxia-induced apoptosis of BMSCs are promising for augmenting the efficacy of BMSC transplantations. Our present study found that under hypoxia, expression of the long non-coding RNA (Lnc), transmembrane protein 235 (Tmem235), was down-regulated, expression of Bcl-2-associated X protein was up-regulated, expression of B-cell lymphoma-2 protein was down-regulated, and the apoptotic rate of BMSCs was over 70%. However, overexpression of Lnc Tmem235 reversed hypoxia-induced apoptosis of BMSCs and promoted their survival. These results demonstrated that Lnc Tmem235 effectively inhibited hypoxia-induced apoptosis of BMSCs. Mechanistically, we found that Lnc Tmem235 exhibited competitive binding to miR-34a-3p with BIRC5 mRNA, which is an inhibitor of apoptosis; this competitive binding relieved the silencing effect of miR-34a-3p on BIRC5 mRNA to ultimately inhibit hypoxia-induced apoptosis of BMSCs by promoting the expression of BIRC5. Furthermore, we co-cultured BMSCs overexpressing Lnc Tmem235 with xenogeneic antigen-extracted cancellous bone to construct tissue-engineered bone to repair a model of early SONFH in vitro. The results showed that overexpression of Lnc Tmem235 effectively reduced apoptosis of BMSCs in the hypoxic microenvironment of osteonecrosis and improved the effect of BMSC transplantation. Taken together, our findings elucidate that Lnc Tmem235 inhibited hypoxia-induced apoptosis of BMSCs by regulating the miR-34a-3p/BIRC5 axis, thus improving the transplantation efficacy of BMSCs for treating early SONFH.

Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

2022 ◽  
Vol 12 (2) ◽  
pp. 273-278
Author(s):  
Daqing Jiang ◽  
Xianxin Xie ◽  
Cong Wang ◽  
Weijie Li ◽  
Jianjun He
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Marrow Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Signaling Activation

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.

Rosmarinic acid protects on rat bone marrow mesenchymal stem cells from hydrogen peroxide-induced apoptosis

2018 ◽  
Vol 20 (6) ◽  
pp. 570-580 ◽  
Author(s):  
Li-Zhen Lin ◽  
Huan-Huan Chen ◽  
Zhou-Xi Lei ◽  
Yun-Rong Li ◽  
Chun-Hua Zhou ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Rosmarinic Acid ◽  
Marrow Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Rat Bone

Expression of ODF and ICAM-1 of Bone Marrow Mesenchymal Stem Cells is Enhanced with Osteogenic Differentiation

2007 ◽  
Vol 361-363 ◽  
pp. 1173-1176
Author(s):  
Jun Wang ◽  
Yu Bo Fan ◽  
Zhi He Zhao ◽  
Juan Li ◽  
Jun Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Early Stage ◽  
Osteoclast Differentiation ◽  
Osteoblastic Differentiation ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Marrow Mesenchymal Stem Cells

Osteoblasts were perceived as pivotal cells, recognized as the cells that control both the formative and the resorptive phases of the bone remodeling cycle. Osteoblasts were an essential requirement for osteoclastogenesis though expressing or secreating bioactive osteoclast-differentiation-regulatory proteins, osteoclast differentiation factor (ODF)was the most important factor among these, ODF participate nearly in every step of differentiation and activation of osteoclasts. In addition, intercellular adhesion molecule-1 (ICAM-1)and its receptors LFA-1 play a role in osteoclast development by affecting adhesion between stromal cells and osteoclast progenitors before the occurrence of ODF-ODF receptor signaling. However, it is not clear about the relationship between ODF, ICAM-1 expression of osteoblasts and differentiation state of osteoblasts. So,the aim of this study was to investgate whether the expression of ODF, ICAM-1 depended on the stage of osteoblastic differentiation from rat bone marrow mesenchymal stem cells(rBMSCs). The viability of rBMSCs is reduced significantly by osteogenic inducement as differentiating into osteoblasts, ALPase activity of OS-treated rBMSCs was enhanced obviously within 9 days , declined subsequently and recovered nearly the original level at day 14. Expression of ODF is enhanced with osteogenic differentiation guadully. whereas, expression of ICAM-1 is activated at OS-treated day 6, then keeping at a stable level. This study indicated that rBMSCs undergoing osteogenic inducement was an ideal model for studying the differentiation and maturation of osteoblasts. During the early stage of differentiation along osteoblasts from stem cells to osteocytes, rBMSCs or Osteoprogenitor react somewhat differently from osteoblasts, suggesting the ability of osteoblasts to regulating differentiation and maturation of osteoclasts have been improved with osteogenic culture.

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