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| 1 | Punicalagin ameliorates collagen-induced arthritis by downregulating M1 macrophage and pyroptosis via NF-κB signaling pathway显示文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease that eventually leads to disability.Inflammatory cell infiltration,severe joint breaking and systemic bone loss are the main clinical symptoms.In this study,we established a collagen-induced arthritis(CIA)model and found a large number of M1 macrophages and pyroptosis,which are important sources of proinflammatory cytokines.Punicalagin(PUN)is an active substance extracted from pomegranate peel.We found that it inhibited joint inflammation,cartilage damage and systemic bone destruction in CIA mice.PUN effectively alleviated the high expression of inflammatory cytokines in synovial tissue in vivo.PUN treatment shifted macrophages from the M1 phenotype to the M2 phenotype after stimulation with lipopolysaccharide(LPS)and interferon(IFN)-γ.The expression of inducible nitric oxide synthase(i NOS)and other proinflammatory cytokines released by M1 macrophages was decreased in the PUN treatment group.However,simultaneously,the expression of markers of anti-inflammatory M2 macrophages,such as arginase(Arg)-1 and interleukin(IL)-10,was increased.In addition,PUN treatment attenuated pyroptosis by downregulating the expression of NLRP3 and caspase-1,thereby preventing inflammatory cell death resulting from the release of IL-1βand IL-18.Mechanistically,PUN inhibited the activation of receptor activators of the nuclear factor-κB(NF-κB)signaling pathway,which contributes to M1 polarization and pyroptosis of macrophages.We concluded that PUN ameliorated pathological inflammation by inhibiting M1 phenotype polarization and pyroptosis and has great potential as a therapeutic treatment for human RA. | Gaoran Ge Jiaxiang Bai Qing Wang Xiaolong Liang Huaqiang Tao Hao Chen Minggang Wei Junjie Niu Huilin Yang Yaozeng Xu Yuefeng Hao Yi Xue Dechun Geng | 2022 | Science China(Life Sciences)2022，65，3： | 14 |
| 2 | ROS signaling cascades:dual regulations for osteoclast and osteoblast显示文摘Accumulating evidence indicates that intracellular reactive oxygen species(ROS)production is highly involved in bone homeostasis by intervening osteoclast or osteoblast differentiation.Interestingly,ROS that are known as oxidizing agents exert dose-dependent biphasic properties in bone remodeling,including preventing osteoblast activity but accelerating osteoclast resorption.ROS mainly composed of superoxide anion radical,hydroxyl radical,nitric oxide,and two-electron reduction product hydrogen peroxide,which are important components to regulate bone cell metabolism and function in mammal skeleton.These free radicals can be partly produced in bone and boosted in an inflammation state.Although numerous researches have emphasized the impacts of ROS on bone cell biology and verified the mechanism of ROS signaling cascades,the recapitulatory commentary is necessary.In this review article,we particularly focus on the regulation of the intracellular ROS and its potential mechanism impacting on cell-signaling transduction in osteoclast and osteoblast differentiation for preferable understanding the pathogenesis and searching for novel therapeutic protocols for human bone diseases. | Huaqiang Tao Gaoran Ge Xiaolong Liang Weicheng Zhang Houyi Sun Meng Li Dechun Geng | 2020 | Acta Biochimica et Biophysica Sinica2020，52，10： | 8 |
| 3 | Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway显示文摘Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles.Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses.Additionally,the NLRP3 inflammasome is activated by prosthetic particles.Sirtuin3,an NAD+-dependent deacetylase of mitochondria,regulates the function of mitochondria in diverse activities.However,whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported.Therefore,we investigated the role of SIRT3 during the process of titanium(Ti)particle-induced osteolysis.We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro.Moreover,we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway.Collectively,these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation. | Kai Zheng Jiaxiang Bai Ning Li Meng Li Houyi Sun Weicheng Zhang Gaoran Ge Xiaolong Liang Huaqiang Tao Yi Xue Yuefeng Hao Chen Zhu Yaozeng Xu Dechun Geng | 2021 | Bioactive Materials2021，6，10： | 5 |
| 4 | Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration显示文摘For patients with osteoporosis,the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation,migration,and osteogenic differentiation abilities of bone marrow mesenchymal stem cells(BMSCs). | Jiaxiang Bai Gaoran Ge Qing Wang Wenming Li Kai Zheng Yaozeng Xu Huilin Yang Guoqing Pan Dechun Geng | 2023 | Research2023，，2： | 0 |
| 5 | Comprehensive overview of microRNA function in rheumatoid arthritis显示文摘MicroRNAs(miRNAs),a class of endogenous single-stranded short noncoding RNAs,have emerged as vital epigenetic regulators of both pathological and physiological processes in animals.They direct fundamental cellular pathways and processes by fine-tuning the expression of multiple genes at the posttranscriptional level.Growing evidence suggests that mi RNAs are implicated in the onset and development of rheumatoid arthritis(RA).RA is a chronic inflammatory disease that mainly affects synovial joints.This common autoimmune disorder is characterized by a complex and multifaceted pathogenesis,and its morbidity,disability and mortality rates remain consistently high.More in-depth insights into the underlying mechanisms of RA are required to address unmet clinical needs and optimize treatment.Herein,we comprehensively review the deregulated mi RNAs and impaired cellular functions in RA to shed light on several aspects of RA pathogenesis,with a focus on excessive inflammation,synovial hyperplasia and progressive joint damage.This review also provides promising targets for innovative therapies of RA.In addition,we discuss the regulatory roles and clinical potential of extracellular mi RNAs in RA,highlighting their prospective applications as diagnostic and predictive biomarkers. | Xiaole Peng Qing Wang Wenming Li Gaoran Ge Jiachen Peng Yaozeng Xu Huilin Yang Jiaxiang Bai Dechun Geng | 2023 | Bone Research2023，11，1： | 0 |
| 6 | Osteoblastic microRNAs in skeletal diseases:Biological functions and therapeutic implications显示文摘Skeletal diseases normally represents a grievous imbalance between osteoblasts for bone formation and osteoclasts for bone resorption.A lack of osteogenic function can make it difficult to repair pathological bone erosion.Therefore,substantial efforts have been made to remedy these issues,with the aid of bioactive molecules,herbs and materials.Following recent insights,the importance of epigenetic gene regulation is increasingly evident,especially microRNAs.MicroRNAs can silence target genes by inhibiting mRNA translation or degrading mRNA molecules by binding to their 3′-untranslated region.There is accumulating evidence indicating that the miRNAs significantly involved in osteogenic gene expression,signaling pathway intervention and programmed cell death.Besides,numerous new target drugs(microRNA inhibitors or agonists)have been proposed to exploit its value in skeletal physiology and pathology.In this review,we mainly discuss the role of microRNAs in the context of skeletal disease-associated osteoblast differentiation,the applications of microRNA polymorphisms as biomarkers for diagnostic and therapeutic targets,and the challenges to meet this goal.Our summary provides novel horizon for improving the therapeutic effect of microRNAs,which may be beneficial to the further clinical translation of microRNAs in the treatments of skeletal diseases. | Lei Yu Wenming Li Peng Yang Wei Zhang Huaqiang Tao Gaoran Ge Huilin Yang Jiaxiang Bai Huaiyu Wang Dechun Geng | 2022 | Engineered Regeneration2022，3，3： | 0 |
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