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Pathological progression of osteoarthritis:a perspective on subchondral bone

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Frontiers of Medicine 2024年第2期18卷 237-257页

作者： Xuefei Li Wenhua Chen Dan Liu Pinghua Chen Shiyun Wang Fangfang Li Qian Chen Shunyi Lv Fangyu Li Chen Chen Suxia Guo Weina Yuan Pan Li Zhijun Hu Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai200032China Research and Development Center of Chinese Medicine Resources and Biotechnology Shanghai University of Traditional Chinese MedicineShanghai201203China

osteoarthritis(OA)is a degenerative bone disease associated with *** rising global aging population has led to a surge in OA cases,thereby imposing a significant socioeconomic *** have been keenly investigating the mechanisms underlying *** studies have suggested that the disease starts with synovial inflammation and hyperplasia,advancing toward cartilage ***,subchondral-bone collapse,sclerosis,and osteophyte formation *** progression is deemed as“top to bottom.”However,recent research is challenging this perspective by indicating that initial changes occur in subchondral bone,precipitating cartilage *** this review,we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone’s physiological state,functions,and the varied pathological shifts during OA *** also introduce the role of multifunctional signal pathways(including osteoprotegerin(OPG)/receptor activator of nuclear factor-kappa B ligand(RANKL)/receptor activator of nuclear factor-kappa B(RANK),and chemokine(CXC motif)ligand 12(CXCL12)/CXC motif chemokine receptor 4(CXCR4))in the pathology of subchondral bone and their role in the“bottom-up”progression of *** vivid pattern maps and clinical images,this review highlights the crucial role of subchondral bone in driving OA progression,illuminating its interplay with the condition.

关键词： osteoarthritis subchondral bone OPG/RANKL/RANK CXCL12/CXCR4

Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

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Bone Research 2024年第2期12卷 438-452页

作者： Bowen Fu Jianlin Shen Xuenong Zou Nian Sun Ze Zhang Zengping Liu Canjun Zeng Huan Liu Wenhua Huang Guangdong Medical Innovation Platform for Translation of 3D Printing Application The Third Affiliated HospitalSouthern Medical UniversityGuangzhou 510630 GuangdongChina Guangdong Engineering Research Center for Translation of Medical 3D Printing Application Guangdong Provincial Key Laboratory of Digital Medicine and BiomechanicsNational Key Discipline of Human AnatomySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510145 GuangdongChina Department of Foot and Ankle Surgery Center for Orthopedic SurgeryThe Third Affiliated HospitalSouthern Medical UniversityGuangzhou 510630 GuangdongChina Department of Orthopedics Affiliated Hospital of Putian UniversityPutian 351100 FujianChina Central Laboratory Affiliated Hospital of Putian UniversityPutian 351100 FujianChina Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongChina Nanfang Hospital Southern Medical UniversityGuangzhou 510515 GuangdongChina Guangzhou Blood Center Guangzhou 510095 GuangdongChina Department of Orthopedics The Affiliated Traditional Chinese Medicine HospitalSouthwest Medical UniversityLuzhou 646000 SichuanChina

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules *** study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)*** demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte *** found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in ***,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in *** findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte *** results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

关键词： chondrocyte osteoarthritis stiffness

Protective Effects of Phellodendron Species on Bone Health: A Novel Perspective on Their Potentials in Treating Osteoporosis and osteoarthritis

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Chinese Journal of Integrative Medicine 2024年第4期30卷 379-384页

作者： XIN Li TAN Guo-yao ZHANG Qiang ZHANG Qun Good Clinical Practice Development Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhou(510630)China Department of Pharmacy Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou(510120)China

Phellodendron(PN)species,traditionally used in Chinese medicine for centuries,hold promise as a potential treatment for osteoporosis(OP)and osteoarthritis(OA)due to their bioactive *** bioactive compounds,including berberine and palmatine,exhibit anti-inflammatory,antioxidant,and bone-protective properties,contributing to their potential therapeutic benefits in promoting bone health and preventing bone ***,challenges such as the need for standardized preparation and dosing,limited clinical studies,and potential interactions with other medications hinder their clinical ***,the rich history of PN species in Chinese medicine provides a promising foundation for future investigation into their potential as alternative treatments for OP and *** research is needed to fully understand the underlying mechanisms of action and explore the clinical implications of PN for bone health.

关键词： Phellodendron species bone health osteoporosis osteoarthritis review

Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p,conferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3528-3542页

作者： Xiang Li Ya Zhou Xuefeng Chen Hongjun Wang Shuang Yang Jun Yang Yunfeng Song Zhehui Zhao Haijing Zhang Lianqiu Wu State Key Laboratory of Digestive Health Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Tide Pharmaceutical Co. Ltd.Beijing 100176China Camford Royal School Beijing 100093China

osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular *** treatments for OA are limited to alleviating various OA *** is a lack of drugs available in clinical practice that can truly repair cartilage ***,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate *** vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA *** prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 *** in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA *** is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.

关键词： Chondroitin sulfate Cartilage osteoarthritis Extracellular matrix Inflammation miRNA p38 MMP13

Advances in the study of mitophagy in osteoarthritis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 197-211页

作者： Hong CAO Xuchang ZHOU Bowen XU Han HU Jianming GUO Miao WANG Nan LI Jun ZOU Department of Sport Rehabilitation Shanghai University of SportShanghai 200438China National Key Laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China School of Sport Medicine and Rehabilitation Beijing Sport UniversityBeijing 100084China

osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of *** initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic *** degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte ***,maintaining mitochondrial homeostasis is an important strategy to mitigate *** is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial *** studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for *** reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

关键词： Mitophagy osteoarthritis Chondrocyte Mitochondria Apoptosis

Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis:a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2024年第2期44卷 243-250页

作者： ZHOU Mingwang DONG Zhuanli WEI Changhao FENG Lufang WANG Xiaoping LIU Haiping JI Xing YANG Kehu LI Shenghua Department of Orthopaedics Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China Department of Quality Management Lanzhou Petrochemical General HospitalLanzhou 730050China Department of Orthopaedics Lanzhou Petrochemical General HospitalLanzhou 730050China Evidence-Based Social Science Research Center School of Public HealthLanzhou UniversityLanzhou730000China Evidence-Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province Lanzhou 730000China Center for Translational Medicine Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730050China Department of Orthopaedics Gansu Provincial Hospital of Traditional Chinese MedicineLanzhou 730000China

OBJECTIVE:To assess the efficacy and safety of extracorporeal shockwave therapy(ESWT)combined with sodium hyaluronate(HA)for the treatment of knee osteoarthritis(KOA).METHODS:PubM ed,Embase,the Cochrane Library,Web of Science,China National Knowledge Infrastructure,Wanfang database,China Science and Technology Journal Database,and SinoMed were searched from inception to July *** quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic *** identified articles were then screened individually using EndnoteX9 for eligibility in this *** heterogeneity among the articles was evaluated using ***:A total of 17 studies,comprising 2000 individuals,were included in this *** results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with *** analysis of clinical efficacy showed that[relative risk(RR)=1.21,95%confidence interval(CI)(1.12,1.30),Posteoarthritis index statistical analysis showed that[SMD=-1.57,95%CI(-2.52,-0.61),P<0.01].Lysholm score statistical analysis showed that[SMD=1.71,95%CI(0.98,2.44),P<0.01].In addition,only minor side effects,such as redness and swelling of the skin,were ***:Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive,welltolerated,safe,and effective method to improve pain and functionality in patients with ***,tightly controlled,randomized,large multicenter trials are warranted to validate the current findings.

关键词： osteoarthritis knee randomized controlled trial extracorporeal shockwave therapy hyaluronic acid Meta-analysis

Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice

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Chinese Journal of Natural Medicines 2024年第2期22卷 137-145页

作者： LIU Mingming GUO Jiatian ZHAO Jing LI Hongye FENG Xiaoxiao LIU Haojun ZHANG Hao JIA Xuejun WEI Rushuai LI Fang CHEN Chong HOU Mingzhuang LV Nanning XU Haiyan Department of human anatomy Xuzhou Medical UniversityXuzhou 221004China Department of Orthopedic Surgery The Affiliated Lianyungang Clinical College of Xuzhou Medical University(The Second People’s Hospital of Lianyungang)Lianyungang 222003China Department of Orthopaedics The First Afliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Institute of Hematology Xuzhou Medical UniversityXuzhou 221004China

Excessive oxidative stress impairs cartilage matrix metabolism balance,significantly contributing to osteoarthritis(OA)***(CSL),a drug derived from Tripterygium wilfordii,has recognized applications in the treatment of cancer and immune system disorders,yet its antioxidative stress mechanisms in OA remain *** study aimed to substantiate CSL’s chondroprotective effects and unravel its underlying *** investigated CSL’s impact on chondrocytes under both normal and inflammatory *** vitro,CSL mitigated interleukin(IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix(ECM)*** vivo,intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA ***,it was found that inhibiting nuclear factor erythroid 2-related factor 2(NRF2)abrogated CSL-mediated antioxidative functions and exacerbated the progression of *** study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2,offering a novel therapeutic avenue for arthritis therapy.

关键词： osteoarthritis Celastrol Articular cartilage Extracellular matrix NRF2

Identifying behavioral determinants and stage of readiness for performing knee massage among individuals with knee osteoarthritis:An observational study

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Journal of Integrative Medicine 2024年第1期22卷 54-63页

作者： Donya Nemati Niki Munk Navin Kaushal College of Nursing the Ohio State UniversityColumbusOH 43210USA Department of Health Sciences School of Health&Human SciencesIndiana UniversityIndianapolisIN 46202USA National Centre for Naturopathic Medicine Southern Cross UniversityLismoreNew South Wales 2480Australia Australian Research Centre in Complementary and Integrative Medicine(ARCCIM) Massage&Myotherapy Australia Fellow and Visiting Faculty of HealthUniversity of Technology SydneyNew South Wales 2007Australia

Objective Patients who experience knee osteoarthritis or chronic knee pain can alleviate their symptoms by performing self-knee *** the readiness and types of determinants needed to facilitate self-knee massage is needed to design effective,theory-informed *** primary objective of this study was to apply the transtheoretical model of behavior change to identify how factors,which include the type of knee condition and pain level,predict an individual’s readiness to adopt self-knee *** secondary objective employed the capability,opportunity and motivation-behavior(COM-B)model to identify relevant determinants that are predictive of an individual’s readiness to undertake self-knee *** An observational study design was used to recruit individuals with knee osteoarthritis(n=270)and chronic knee pain(n=130).Participants completed an online survey that assessed the transtheoretical model of behavior change stages,COM-B determinants(capability,opportunity and motivation),along with self-administered massage *** analysis of covariance and structural equation modeling were used to test the primary and secondary objective,*** Participants who had knee osteoarthritis scored higher on the action stage compared to those with chronic pain(P=0.003),and those who experienced greater level of pain scored higher in the contemplation(P<0.001)and action phases(P<0.001)of performing knee massage compared to those with milder *** COM-B structural equation model revealed self-administered knee massage to be predicted by capability(β=0.31,P=0.004)and motivation(β=0.29,P<0.001),but not opportunity(β=–0.10,P=0.39).Pain level predicted motivation(β=0.27,P<0.001),but not capability(β=0.09,P=0.07)or opportunity(β=0.01,P=0.83).Tests for mediating effects found that determinants of COM-B(motivation and capability)mediate between pain level and self-administered massage behavior(β=0.10,P=0.002).Conclusion Cl

关键词： osteoarthritis Massage Self-management Transtheoretical model of behavior change Behavioral model

Current therapies for osteoarthritis and prospects of CRISPR-based genome,epigenome,and RNA editing in osteoarthritis treatment

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Journal of Genetics and Genomics 2024年第2期51卷 159-183页

作者： Yuxi Chen Xiao Luo Rui Kang Kaixin Cui Jianping Ou Xiya Zhang Puping Liang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Center for Reproductive Medicine The Third Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhouGuangdong 510630China

osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of *** balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of ***,there is a lack of effective therapeutic strategies for OA *** the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory *** by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA *** review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA ***,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.

关键词： osteoarthritis Genome editing Epigenone editing RNA editing