Chromodomain helicase DNA-binding protein 5 (CHD5) plays a crucial tumor suppressor role in multiple types of tumors. For this study, we investigated its clinical significance and the molecular mechanism(s) underlying tumorigenesis in renal cell carcinoma (RCC). Initially, CHD5 expression was assessed in primary tumor tissue and in tissue array. Correlations among CHD5 expression and clinicopathological characteristics were analyzed. Next, lentivirus-mediated CHD5 overexpression in the ACHN and 769-P cells was used to assess effects on proliferation, migration, invasion ability, and the regulation of the p14ARF/p53 and p16INK4a/RB signaling pathways. Finally, a xenograft mouse model was used to verify its impact on tumor growth in vivo. Results demonstrated that CHD5 was downregulated in tumor tissues and that low CHD5 expression was correlated with advanced TNM stage, high Fuhrman grade, lymph node metastasis, and poor survival. Overexpression of CHD5 inhibited proliferation, migration, and invasion in vitro; prompted cell cycle G1 phase arrest; induced apoptosis; and suppressed tumor growth in vivo. Furthermore, we confirmed that CHD5 activates the p53 and RB pathways to inhibit tumorigenesis in RCC. In summary, CHD5 is involved in the initiation and progression of RCC and may serve as a diagnostic biomarker and a potential therapeutic target for RCC.

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Background Osteoarthritis (OA) is a chronic disease that can cause disability. The prevalence of osteoarthritis has increased year by year, become a disease that mainly causes the elderly to suffer. With the increasing understanding of bone marrow mesenchymal stem cell (BMSC) in tissue repair, BMSCs shown good therapeutic effects in OA, it may be due to BMSCs exerted their capacities of differentiation, secretion and immunoregulatory in the joints. As previous describe, BMSCs culture supernatant is proved that rich in multiple cytokines. Therefore, how BMSCs injection therapy exerts its ability to exert therapeutic effects, and whether its therapeutic effect can be replaced by its culture supernatant has become the focus of this article. Methods In vitro, we designed a co-culture system to deepen understand this new stem cell therapy. Through two kinds of cells cultured alone, direct and indirect cell contact co-culture to observe changes in cell morphology, quantity and cytoplasmic glycoprotein of these two types of cells and changes of the level of growth factor in the culture supernatant to explore the interaction of these two types of cells; in vivo, we induced an OA model and Injected Saline solution, BMSCs and their culture supernatants respectively for treatment, then we compared the improvement results of OA by evaluating changes in the cartilage layer after different treatments. And determine the changes of some growth factors and inflammatory factors in synovial fluid to analyze the possible mechanisms of multiple treatments. Result In the co-culture system, it was found that the direct co-culture of BMSCs and OCs can enhance the proliferation ability of OCs, OCs can retain more cytoplasmic glycoprotein, and BMSCs did not occurred abnormal differentiation during the co-culture. In animal experiments, it was found that the ability of BMSCs injection treatment has obvious therapeutic effect on OA, and the effect is better than its supernatant injection treatment. BMSCs therapy reduced matrix loss in articular cartilage cells, and reduced type I collagen production and fibrosis on articular cartilage, effectively regulating EGF and TGF-β1change and inhibited intra-articular inflammation. Supernatant injection treatment will not significantly delay the progress of OA, and it cannot replace BMSCs for the treatment of OA. Conclusion BMSCs therapy is a potential new therapy for OA. The secretion and regulation ability of BMSCs plays an important role in the treatment process. BMSCs are activated by the intra-articular environment of OA, regulating growth factors such as EGF and TGFβ to promote articular cartilage regeneration, and reducing intra-articular inflammation by regulating inflammatory factors and delaying the progression of OA. These effects cannot be replaced by the culture supernatant which is rich in multiple factors, and its regulation function requires the presence of BMSCs. These results provide a relatively comprehensive understanding of BMSCs cell therapy in OA and provide a new explanation for the possible anti-inflammatory effects of BMSCs in the joint.

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Background: Chromodomain helicase DNA binding protein 5 (CHD5) was reported to be a tumor suppressor and our previous work showed CHD5 was epigenetically inactivated in human chronic myeloid leukemia (CML). This study aimed to investigate the effect of its overexpression on CML tumorigenesis. Methods: Quantitative reverse-transcriptase PCR and Western blotting analysis were used to detect the expression of CHD5 in human CML cell lines. The endogenous CHD5 expression was activated in two CML cell lines by CRISPR/dCas9-SAM system. In vitro cell function experiments were performed including proliferation, colony formation, apoptosis, autophagy, senescence and differentiation assays. Furthermore, tumorigenicity was evaluated in vivo in nude mice xenograft model. Results: CHD5 was down-regulated in CML cell lines compare to normal bone marrow mononuclear cells (MCs). Cell proliferation after activating CHD5 was significantly inhibited. Moreover, overexpression of CHD5 induced G2/M phase arrest and apoptosis in CML cells. In a tumor xenograft mouse model, CHD5 restoration was found to sharply repress tumor growth. Compared with the control group, overexpression of CHD5 enhanced the expression of p21 and cdc2 phosphorylation, whereas decreased the protein level of Cyclin B1. Furthermore, experiments revealed that up-regulation of CHD5 activated caspase-3, while antiapoptosis protein Bcl-2 expression was reduced in CML cells. Conclusions: CHD5 plays a role of anti-tumorigenic effects involved in CML cell proliferation, cell cycle arrest and apoptosis.