Intervertebral disc degeneration (IVDD) is a main cause of low back pain that is associated with extracellular matrix (ECM) degradation and inflammation. This study aims to investigate the role of DNMT3B and its regulatory mechanisms in IVDD. IVDD rat models were constructed followed by transfections with oe-DNMT3B or oe-YAP in order to explore the role of DNMT3B in the development of IVDD. After that transfection, nucleus pulposus (NP) cells were isolated and transfected with oe-DNMT3B, oe-TRPA1, si-YAP, oe-YAP or oe-COX2 in order to investigate the functions of DNMT3B in NP cells. DNMT3B was poorly expressed in IVDD tissues and NP cells whereas TRPA1, COX2, and YAP were highly expressed. The proliferation or apoptosis of NP cells was detected through CCK-8 assay or flow cytometry, respectively. Overexpression of DNMT3B promoted the proliferation of NP cells, inhibited their apoptosis, as well as increasing the expression of collagen II and aggrecan and decreasing expression of MMP3 and MMP9. Besides, DNMT3B suppressed inflammation and alleviated IVDD. Mechanistically, DNMT3B modified the TRPA1 promoter by methylation to inhibit the expression of COX2. Overexpression of COX2 promoted the apoptosis of NP cells and decreased the expression of YAP, which was reversed by upregulating DNMT3B. DNMT3B may promote the proliferation of NP cells and prevent their ECM degradation through the TRPA1/COX2/YAP axis, thereby alleviating IVDD in rats.
Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought “Yin-Yang theory” in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS.
Bone remodeling participates in osteoporosis (OP). Silent information regulating factor 2 related enzyme 1 (sirtuin1, SIRT1) regulates cell survival, differentiation, metabolism and inflammation. However, the regulatory effect of SIRT1 on the formation of osteoblasts and osteoclasts has not been reported. OP and normal rat BMSCs were assigned into control group, OP group, and SIRT1 group (Resveratrol) followed by measuring cell proliferation by MTT assay, ALP activity, expression of SIRT1, RUNX2 and OP by Real time PCR, AKT/β-catenin signaling protein expression by Western blot. Rat BMSCs were cultured and treated with RANKL to induce osteoclast culture in the presence or absence of Resveratrol followed by analysis of cell proliferation and c-Fos and TRAP expression. SIRT1 expression and secretion in BMSCs cells and supernatant of OP group were significantly reduced and cell proliferation was significantly inhibited along with reduced RUNX2 and OP expression, ALP activity as well as decreased AKT/β-catenin phosphorylation compared to control group (P < 0.05); addition of Resveratrol can significantly reverse the above changes (P <0.05). Resveratrol can significantly promote SIRT1 expression, inhibit osteoclast proliferation, and reduce c-Fos and TRAP expression (P < 0.05). SIRT1 expression is reduced in osteoporosis and its upregulation promotes osteogenesis through AKT/β-catenin pathway, inhibits osteoclast formation, and improves osteoporosis.
Our study intends to explore the effect of bone marrow mesenchymal stem cells (BMSCs) on neuronal activity and GDNF expression in rats with SCI. Rats were assigned into spinal cord injury group (group S); routinely control group (group R) without spinal incision; and BMSCs group (group B) which received BMSCs treatment with n = 4 rats in each group. The neuronal cell proliferation was detected by cck-8 method, BBB score was used to detect lower limb motor function, GDNF mRNA expression was detected by qRT-PCR, GDNF protein positive expression was measured by immunohistochemistry and cell invasion was assessed by Transwell. Group B rats showed significantly higher BBB score higher than group S (P <0.05) and group R rats had higher score than group B (P <0.05). The OD value of cell proliferation in group R was significantly higher than group S and group B (P <0.05). Group R had the largest number of neuronal cell proliferation followed by group B and group S (P <0.05); the neuronal cell invasion ability of group S and group B was decreased significantly compared with Group R (all P <0.05); group B rat showed higher neuronal cell invasion ability than group S (P <0.05). The GDNF mRNA expression in group B was higher than group S (P <0.05) and lower than group R (P <0.05). The positive number of GDNF protein in group B was higher than group S (P <0.05) and lower than group R (P <0.05). In conclusion, BMSCs can significantly improve the decline of cell activity and motor capacity caused by acute SCI in rats, and can enhance the neuronal cells activity possibly by increasing GDNF expression in neuronal cells and improving their lower limbs motor function.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.