Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells(SSCs).The mechanisms underlying the transition from SSCs to sperm are largely unknown.Most stud...Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells(SSCs).The mechanisms underlying the transition from SSCs to sperm are largely unknown.Most studies utilize gene knockout mice to explain the mechanisms.However,the production of genetically engineered mice is costly and time-consuming.In this study,we presented a convenient research strategy using an RNA interference(RNAi)and testicular transplantation approach.Histone H3 lysine 9(H3K9)methylation was dynamically regulated during spermatogenesis.As Jumonji domain-containing protein 1A(JMJD1A)and Jumonji domain-containing protein 2C(JMJD2C)demethylases catalyze histone H3 lysine 9 dimethylation(H3K9me2),we firstly analyzed the expression profile of the two demethylases and then investigated their function.Using the convenient research strategy,we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases.These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.展开更多
Objective To investigate the treatment effect of the histone demethylase inhibitor GSK-J4,a small molecule that inhibits the demethylase activity of Jumonji domain-containing protein 3(JMJD3),in the treatment of perio...Objective To investigate the treatment effect of the histone demethylase inhibitor GSK-J4,a small molecule that inhibits the demethylase activity of Jumonji domain-containing protein 3(JMJD3),in the treatment of periodontitis.Methods Gingival tissues from patients with moderate to severe chronic periodontitis and healthy controls were collected to evaluate JMJD3 expression via real-time quantitative reverse transcription PCR(RT-qPCR)and immunohistochemistry(IHC).Next,Sprague–Dawley(SD)rats were used to investigate the effect of GSK-J4 in vivo.The experimental periodontitis model was induced by upper first molar ligation and gingival sulcus injection of Porphyromonas gingivalis.The rats were divided into a healthy group,a periodontitis group,periodontitis plus GSK-J4 treatment groups(P+GSK-J415 mg/kg or 25 mg/kg),and a periodontitis plus dimethyl sulfoxide(DMSO)group(P+DMSO).After 4 weeks,maxillary molar segments were assessed via micro-computed tomography(CT)and hematoxylin and eosin(HE)staining.Serum tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay(ELISA).Results Higher expression of the Jmjd3 gene and JMJD3 protein was detected in human inflamed gingiva than in healthy gingiva(P<0.05).GSK-J4 administration reversed alveolar bone absorption[i.e.,reduced alveolar bone crest(ABC)-cementoenamel junction(CEJ)distance],reduced inflammatory cell accumulation at the crest of the alveolar bone,and alleviated serum TNF-αlevels in rats with periodontitis.Moreover,the number of H3K27me3-positive nuclei was greater in model rats treated with GSK J4 than in model rats.Conclusions The histone demethylase inhibitor GSK-J4 attenuated periodontal bone loss and inflammation in a rat periodontitis model by targeting JMJD3.展开更多
基金financially supported by the Shandong Provincial Natural Science Foundation(No.ZR2021QC182).
文摘Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells(SSCs).The mechanisms underlying the transition from SSCs to sperm are largely unknown.Most studies utilize gene knockout mice to explain the mechanisms.However,the production of genetically engineered mice is costly and time-consuming.In this study,we presented a convenient research strategy using an RNA interference(RNAi)and testicular transplantation approach.Histone H3 lysine 9(H3K9)methylation was dynamically regulated during spermatogenesis.As Jumonji domain-containing protein 1A(JMJD1A)and Jumonji domain-containing protein 2C(JMJD2C)demethylases catalyze histone H3 lysine 9 dimethylation(H3K9me2),we firstly analyzed the expression profile of the two demethylases and then investigated their function.Using the convenient research strategy,we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases.These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
基金supported by the Tianjin Stomatological Hospital MD and PhD Key Program(No.2019BSZD11)Periodontal Key Discipline Project of Tianjin Stomatological Hospital(2022P02)+1 种基金the Science and Technology Project of Tianjin Health Commission(No.ZC20039)the High-level Talents in the Medical/Health Care Industry-Young Medical Elites(No.TJSQNYXXR-D2-114).
文摘Objective To investigate the treatment effect of the histone demethylase inhibitor GSK-J4,a small molecule that inhibits the demethylase activity of Jumonji domain-containing protein 3(JMJD3),in the treatment of periodontitis.Methods Gingival tissues from patients with moderate to severe chronic periodontitis and healthy controls were collected to evaluate JMJD3 expression via real-time quantitative reverse transcription PCR(RT-qPCR)and immunohistochemistry(IHC).Next,Sprague–Dawley(SD)rats were used to investigate the effect of GSK-J4 in vivo.The experimental periodontitis model was induced by upper first molar ligation and gingival sulcus injection of Porphyromonas gingivalis.The rats were divided into a healthy group,a periodontitis group,periodontitis plus GSK-J4 treatment groups(P+GSK-J415 mg/kg or 25 mg/kg),and a periodontitis plus dimethyl sulfoxide(DMSO)group(P+DMSO).After 4 weeks,maxillary molar segments were assessed via micro-computed tomography(CT)and hematoxylin and eosin(HE)staining.Serum tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay(ELISA).Results Higher expression of the Jmjd3 gene and JMJD3 protein was detected in human inflamed gingiva than in healthy gingiva(P<0.05).GSK-J4 administration reversed alveolar bone absorption[i.e.,reduced alveolar bone crest(ABC)-cementoenamel junction(CEJ)distance],reduced inflammatory cell accumulation at the crest of the alveolar bone,and alleviated serum TNF-αlevels in rats with periodontitis.Moreover,the number of H3K27me3-positive nuclei was greater in model rats treated with GSK J4 than in model rats.Conclusions The histone demethylase inhibitor GSK-J4 attenuated periodontal bone loss and inflammation in a rat periodontitis model by targeting JMJD3.
文摘目的 :探讨组蛋白去甲基化酶JMJD2B影响人结直肠癌细胞恶性表型所介导的信号通路。方法 :以RNA干扰技术靶向沉默人结直肠癌细胞HCT116和SW480中JMJD2B的表达,采用蛋白质印迹法检测人结直肠癌细胞ERK-MAPK信号通路的变化,并分别采用CCK-8、流式细胞分析检测细胞增殖和细胞周期分布、凋亡情况。结果:转染JMJD2B si RNA能特异性抑制JMJD2B的表达并导致ERK2表达下调,其磷酸化水平也降低,肿瘤细胞发生G2/M或G0/G1期阻滞,细胞凋亡比例增加,增殖显著受抑(P<0.05)。结论:抑制JMJD2B可通过阻断ERK-MAPK信号转导而抑制人结直肠癌细胞的恶性表型。
