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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 | 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 |
| 3 | Rational integration of defense and repair synergy on PEEK osteoimplants via biomimetic peptide clicking strategy显示文摘Polyetheretherketone(PEEK)has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance.However,its biological inertness,poor osteoinduction,and weak antibacterial activity make the clinical applications in a dilemma.Inspired by the mussel adhesion mechanism,here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins(Mfps)-mimic peptide with clickable azido terminal.The peptide enables mussel-like adhesion on PEEK biomaterial surfaces,leaving azido groups for the further steps of biofunctionalizations.In this study,antimicrobial peptide(AMP)and osteogenic growth peptide(OGP)were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair.Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios,an optimal PEEK surface was finally obtained in this research,which could long-term inhibit bacterial growth,stabilize bone homeostasis and facilitate interfacial bone regeneration.In a word,this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants,in particular,achieving rational integration of multiple biofunctions to match clinical requirements. | Meng Li Jiaxiang Bai Huaqiang Tao Li Hao Weiling Yin Xiaoxue Ren Ang Gao Ning Li Miao Wang Shiyuan Fang Yaozeng Xu Liang Chen Huilin Yang Huaiyu Wang Guoqing Pan Dechun Geng | 2022 | Bioactive Materials2022，7，2： | 2 |
| 4 | Targeting strategies for bone diseases:signaling pathways and clinical studies显示文摘Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago,tremendous advances have occurred in targeted therapy.From the initial selective antibody,antitoxin to targeted drug delivery that emerged in the past decades,more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases.As a highly pyknotic mineralized tissue with lessened blood flow,bone is characterized by a complex remodeling and homeostatic regulation mechanism,which makes drug therapy for skeletal diseases more challenging than other tissues.Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks.With the deepening understanding of bone biology,improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon.In this review,we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting.We highlight targeting strategies based on bone structure and remodeling biology.For bone-targeted therapeutic agents,in addition to improvements of the classic denosumab,romosozumab,and PTH1R ligands,potential regulation of the remodeling process targeting other key membrane expressions,cellular crosstalk,and gene expression,of all bone cells has been exploited.For bone-targeted drug delivery,different delivery strategies targeting bone matrix,bone marrow,and specific bone cells are summarized with a comparison between different targeting ligands.Ultimately,this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area. | Hao Xu Wentao Wang Xin Liu Wei Huang Chen Zhu Yaozeng Xu Huilin Yang Jiaxiang Bai Dechun Geng | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 2 |
| 5 | 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 |
| 6 | 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 |
| 7 | Nanomaterial-assisted theranosis of bone diseases显示文摘Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction.Conventional approaches can regulate bone homeostasis to a certain extent.However,these therapies are still associated with some undesirable problems.Fortunately,recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related diseases.This review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related diseases.First,the potential utility of nanomaterials for biological imaging and biomarker detection is illustrated.Second,nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are highlighted.Finally,perspectives in this field are offered,including current key bottlenecks and future directions,which may be helpful for exploiting nanomaterials with novel properties and unique functions.This review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases. | Kai Zheng Jiaxiang Bai Huilin Yang Yaozeng Xu Guoqing Pan Huaiyu Wang Dechun Geng | 2023 | Bioactive Materials2023，，6： | 0 |
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