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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

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膝关节软骨缺损的微骨折软骨面重建手术技术

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骨科动态 2007年第1期3卷 49-57页

作者： KAI MITHOEFER RILEY J. WILLIAMS Ⅲ RUSSELL F. WARREN HOLLIS G. POTTER CHRISTOPHER R. SPOCK EDWARD C. JONES THOMAS L. WICKIEWICZ ROBERT G. MARX 张春礼（译） investigtion performed at the institute for cartilage repair Hospital for Special Surgery New York NY The original scientific article in which the surgical technique was presented was published in JBJS Vol. 87-A pp 1911-1920 September 2005 西安第四军医大学西京医院骨科 710032

背景：微骨折是常用于修复膝关节软骨病损的技术。尽管该项技术应用很普遍，但有关远期临床结果的信息仍很有限。本研究的目的是找出该项软骨修复技术临床疗效的影响因素。方法：采用微骨折技术治疗48例膝关节稳定、股骨髁孤立、全层软... 详细信息

背景：微骨折是常用于修复膝关节软骨病损的技术。尽管该项技术应用很普遍，但有关远期临床结果的信息仍很有限。本研究的目的是找出该项软骨修复技术临床疗效的影响因素。方法：采用微骨折技术治疗48例膝关节稳定、股骨髁孤立、全层软骨缺损并有症状的患者。最短随访24个月，采用公认的疗效评分和主观临床评级及软骨敏感NRI扫描对患者的结果进行前瞻性评估。结果：末次随访时，膝关节功能优、良32例（67％），可12例（25％），差4例（8％）。日常活动评分、国际膝关节信息委员会（IKDC）评分、SF-36体格检查评分术后均有显著性增加（p〈0.05），体重指数（BM）较低，则日常活动评分SF-36体格检查评分较高，BMI〉30kg/m^2则效果最差。术前症状时间少于12个月，则日常活动评分显著增加（p〈0.05）。24膝中MRI证实缺损填充，修复良好13例（54%），中等填充7例（29%），填充不良4例（17%），填充度与膝关节功能评分相关。全部缺损填充良好的膝关节，功能均有改善，而填充不良的关节，功能改善有限，且24个月后功能评分下降。结论：微骨折技术修复膝关节软骨病损在最短2年的随访期间功能有显著改善，软骨缺损填充良好，BMI较低，术前症状期短者可取得最佳短期疗效；高BMI对短期疗效有负面影响，软件缺损填充不良则短期疗效较差。

关键词：膝关节软骨缺损软骨面重建微骨折手术技术膝关节软骨病损功能评分膝关节功能 SF-36

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High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

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World Journal of Stem Cells 2024年第2期16卷 176-190页

作者： Yu-Su Wang Wen-Hui Chu Jing-Jie Zhai Wen-Ying Wang Zhong-Mei He Quan-Min Zhao Chun-Yi Li institute of Antler Science and Product Technology Changchun Sci-Tech UniversityChangchun 130000Jilin ProvinceChina College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118Jilin ProvinceChina School of Life Science Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina Department of Oral Implantology Hospital of StomatologyJilin UniversityChangchun 130000Jilin ProvinceChina

BACKGROUND cartilage defects are some of the most common causes of *** lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral *** studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral *** To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral *** We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM *** sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the *** weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee *** The defects were successfully repaired by applying the *** highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem *** Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

关键词： Osteochondral defect repair Mesenchymal stem cells Extracellular matrix Decellularization Antler stem cells Reserve mesenchymal cells Xenogeneic

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Systematic review on the use of autologous matrix-induced chondrogenesis for the repair of articular cartilage defects in patients

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World Journal of Orthopedics 2017年第7期8卷 588-601页

作者： Nafisa Shaikh Matthew K T Seah Wasim S Khan SAS Facility Faculty of Science University of TechnologySydney Department of Trauma and Orthopaedics Addenbrookes Hospital University College London institute of Orthopaedics and Musculoskeletal Sciences Royal National Orthopaedic Hospital

AIM To systematically review the results of studies looking at autologous matrix-induced chondrogenesis(AMIC) in humans. METHODS A literature search was performed, adhering to the PRISMA guidelines, to review any studies using such techniques in humans. Our initial search retrieved 297 articles listed on MEDLINE, Google Scholar, CINHal and EMBASE. From these studies, 15 studies meeting the eligibility criteria were selected and formed the basis of our systematic *** The study designs, surgical techniques and outcome measures varied between the studies. Although all studies reported improvements in patient outcome measures, this was not necessarily correlated with magnetic resonance imaging findings. Although there were many additional procedures performed, when AMIC was performed in isolation, the results tended to peak at 24 mo before declining. CONCLUSION Although short-term studies suggest improved patient reported outcomes with a variety of scaffolds, surgical techniques and rehabilitation regimes, the literature remains equivocal on whether the defect size and location, and patient factors affect the outcome. Patientbenefit appears to be maintained in the short-tomedium term but more high level studies with extensive and robust validated outcome measures should be conducted to evaluate the medium-and long-term effect of the AMIC procedure.

关键词： Autologous matrix-induced chondrogenesis cartilage defects Humans,PRISMA

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Mesenchymal stem cell enhances chondral defects healing in horses

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Stem Cell Discovery 2013年第4期3卷 218-225页

作者： Ana Lucia Miluzzi Yamada Armando de Mattos Carvalho Andrei Moroz Elenice Deffune Marcos Jun Watanabe Carlos Alberto Hussni Celso Antonio Rodrigues Ana Liz Garcia Alves Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science(FMVZ)UNESPUniversidade Estadual PaulistaBotucatuBrazil Faculty of Veterinary Medicine Cuiaba UniversityCuiabaBrazil Department of Morphology Institute of BiosciencesUNESPBotucatuBrazil Blood Center School of MedicineUNESPBotucatuBrazil

The purpose of this study was to evaluate the effect of intralesional Mesenchymal Stem Cells (MSC) on the treatment of experimentally induced articular chondral defects in horses, emphasizing the benefits of this application in veterinary medicine. Chondral defects were induced in the medial femoral trochlea of both hind limbs of four horses. Thirty days post induction;the horses were divided into two groups. The G1 was submitted to treatment with MSC and the G2 was the control group. Clinical evaluations, synovial fluid analysis and synovial Prostaglandin E2 (PGE2) assessment were performed prior to defects and fortnightly up to 120 and 150 days. Macroscopic, histopathological and histochemical evaluations were performed at the end of the experiment. The treatment with MSC reduced the intraarticular inflammatory process. The G1 showed lower PGE2 concentrations in the synovial fluid and greater percentage of mononuclear cells and lower percentages of lymphocytes and neutrophils. The treatment improved the macro and microscopic aspects of repair tissue. No difference was observed in the scores of lameness between the G1 and G2. The use of MSC in the treatment of chondral defects minimized joint inflammation, as confirmed by synovial fluid analysis. The treatment resulted in an improved repair tissue, verified by macroscopic examination, histochemical and histopathological analysis.

关键词： Arthroscopy cartilage Equine Lameness Mesenchymal Stem Cells

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Comparative effectiveness of adipose-derived mesenchymal stromal cells in the management of knee osteoarthritis:A meta-analysis

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World Journal of Orthopedics 2023年第1期14卷 23-41页

作者： Sathish Muthu Sandesh C Patil Naveen Jeyaraman Madhan Jeyaraman Prakash Gangadaran Ramya Lakshmi Rajendran Eun Jung Oh Manish Khanna Ho Yun Chung Byeong-Cheol Ahn Department of Orthopaedics Government Medical College and HospitalDindigul 624001Tamil NaduIndia Department of Biotechnology School of Engineering and TechnologySharda UniversityGreater Noida 201310Uttar PradeshIndia Jeyaraman Research AssociateOrthopaedic Research GroupCoimbatore 641045Tamil NaduIndia Indian Stem Cell Study Group Association Lucknow 226001Uttar PradeshIndia Department of Orthopaedic Rheumatology Dr.RML National Law UniversityLucknow 226012Uttar PradeshIndia ACS Medical College&Hospital Dr MGR Educational and Research InstituteChennai 600056Tamil NaduIndia BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents Department of Biomedical SciencesSchool of MedicineKyungpook National UniversityDaegu 41944South Korea Department of Nuclear Medicine School of MedicineKyungpook National UniversityDaegu 41944South Korea Department of Plastic and Reconstructive Surgery CMRIKyungpook National UniversityKyungpook National University HospitalDaegu 41944South Korea Department of Plastic and Reconstructive Surgery School of MedicineKyungpook National UniversityDaegu 41944South Korea Department of Nuclear Medicine Kyungpook National University HospitalDaegu 41944South Korea

BACKGROUND Osteoarthritis(OA)is the most common joint disorder,is associated with an increasing socioeconomic impact owing to the ageing *** To analyze and compare the efficacy and safety of bone-marrow-derived mesenchymal stromal cells(BM-MSCs)and adipose tissue-derived MSCs(AD-MSCs)in knee OA management from published randomized controlled trials(RCTs).METHODS Independent and duplicate electronic database searches were performed,including PubMed,EMBASE,Web of Science,and Cochrane Library,until August 2021 for RCTs that analyzed the efficacy and safety of AD-MSCs and BM-MSCs in the management of knee *** visual analog scale(VAS)score for pain,Western Ontario McMaster Universities Osteoarthritis Index(WOMAC),Lysholm score,Tegner score,magnetic resonance observation of cartilage repair tissue score,knee osteoarthritis outcome score(KOOS),and adverse events were *** was performed on the R-platform using OpenMeta(Analyst)***-one studies,involving 936 patients,were *** one study compared the two MSC sources without patient randomization;hence,the results of all included studies from both sources were pooled,and a comparative critical analysis was *** At six months,both AD-MSCs and BM-MSCs showed significant VAS improvement(P=0.015,P=0.012);this was inconsistent at 1 year for BM-MSCs(Pperformed BM-MSCs compared to controls in measures such as WOMAC(P<0.001,P=0.541),Lysholm scores(P=0.006;P=0.933),and KOOS(P=0.002;P=0.012).BM-MSC-related procedures caused significant adverse events(P=0.003)compared to AD-MSCs(P=0.673).CONCLUSION Adipose tissue is superior to bone marrow because of its safety and consistent efficacy in improving pain and functional *** trials are urgently warranted to validate our findings and reach a consensus on the ideal source of MSCs for managing knee OA.

关键词： Mesenchymal stromal cell Adipose tissue-derived mesenchymal stromal cell Bone-marrow derived mesenchymal stromal cell cartilage regeneration Knee osteoarthritis Meta-analysis Efficacy Safety

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Small extracellular vesicles in combination with sleep-related circRNA3503:A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis

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Bioactive Materials 2021年第12期6卷 4455-4469页

作者： Shi-Cong Tao Ji-Yan Huang Yuan Gao Zi-Xiang Li Zhan-Ying Wei Helen Dawes Shang-Chun Guo Department of Orthopaedic Surgery Shanghai Jiao Tong University Affiliated Sixth People’s Hospital600 Yishan RoadShanghai200233China institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People’s Hospital600 Yishan RoadShanghai200233China Department of Stomatology Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine185 Pu’an RoadShanghai200021China School of Medicine Shanghai Jiao Tong University227 South Chongqing RoadShanghai200025China Medical College of Soochow University Soochow UniversityChangzhou215123JiangsuChina Shanghai Clinical Research Centre of Bone Diseases Department of Osteoporosis and Bone DiseasesShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Faculty of Health and Life Science Oxford Brookes UniversityHeadington RoadOxfordOX30BPUK

Osteoarthritis(OA),characterized by chondrocyte apoptosis and disturbance of the balance between catabolism and anabolism of the extracellular matrix(ECM),is the most common age-related degenerative joint disease *** sleep has been found to be beneficial for cartilage repair,and circular RNAs(circRNAs)have been demonstrated to be involved in the pathogenesis of OA,we performed RNA sequencing(RNA-seq),and found circRNA3503 was significantly increased after melatonin(MT)-induced cell *** of circRNA3503 expression completely rescued the effects of interleukin-1β(IL-1β),which was used to simulate OA,on apoptosis,ECM degradation-and synthesis-related ***,circRNA3503 acted as a sponge of hsa-miR-181c-3p and ***,as we previously showed that small extracellular vesicles(sEVs)derived from synovium mesenchymal stem cells(SMSCs)can not only successfully deliver nucleic acids to chondrocytes,but also effectively promote chondrocyte proliferation and migration,we assessed the feasibility of sEVs in combination with sleep-related circRNA3503 as an OA *** successfully produced and isolated circRNA3503-loaded sEVs(circRNA3503-OE-sEVs)from ***,poly(D,L-lactide)-b-poly(ethylene glycol)-b-poly(D,L-lactide)(PDLLA-PEG-PDLLA,PLEL)triblock copolymer gels were used as carriers of *** in vivo and in vitro experiments,PLEL@circRNA3503-OE-sEVs were shown to be a highly-effective therapeutic strategy to prevent OA *** multiple pathways,circRNA3503-OE-sEVs alleviated inflammation-induced apoptosis and the imbalance between ECM synthesis and ECM degradation by acting as a sponge of hsa-miR-181c-3p and *** addition,circRNA3503-OE-sEVs promoted chondrocyte renewal to alleviate the progressive loss of *** results highlight the potential of PLEL@circRNA3503-OE-sEVs for preventing OA progression.

关键词： Extracellular vesicles Exosomes Circular RNAs PDLLA-PEG-PDLLA

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γ射线辐照交联PVA水凝胶关节软骨修复材料的结构与性能研究

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医用生物力学 2009年第5期24卷 347-351页

作者：马如银熊党生彭艳金加波 Laura McCann Zhongmin Jin John Fisher 南京理工大学材料科学与工程系南京210094 institute of Medical and Biological Engineering School of Mechanical Engineering The University of Leeds Leeds UK LS2 9JT

目的研究制备工艺对γ射线辐照交联PVA水凝胶关节软骨修复材料的结构与摩擦学性能的影响,为其在关节软骨损伤修复领域的应用提供理论基础。方法采用冷冻解冻和辐照交联相结合的方法制备聚乙烯醇(PVA)水凝胶,研究其微观形貌、含水量及与... 详细信息

目的研究制备工艺对γ射线辐照交联PVA水凝胶关节软骨修复材料的结构与摩擦学性能的影响,为其在关节软骨损伤修复领域的应用提供理论基础。方法采用冷冻解冻和辐照交联相结合的方法制备聚乙烯醇(PVA)水凝胶,研究其微观形貌、含水量及与自然软骨配副的摩擦学性能。结果(1)微观结构的观察表明,制备的PVA水凝胶具有三维多孔网络结构,辐照交联使得网络结构更加致密和完善;(2)水凝胶的含水量随着辐照剂量和PVA浓度的增加而减小;(3)在往复式销-盘摩擦磨损试验机上,研究本水凝胶材料与自然关节软骨配副时的摩擦学性能,结果表明,摩擦的起始阶段,双相润滑机制其主导作用,载荷主要由水凝胶中的液体相所承担,摩擦系数较小,随着载荷作用时间的延长,固体相所承受载荷的比例相对增高,摩擦系数渐渐增大且趋于稳定,润滑机制转为边界润滑。摩擦系数随着辐照剂量和PVA浓度的增加而减小。

关键词：聚乙烯醇水凝胶软骨修复摩擦性能

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