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Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability. 使用新型高功能牛胶原蛋白肽作为营养疗法治疗和改善成人膝关节骨关节炎:一项评估疗效、安全性和耐受性的双盲、前瞻性、多中心、随机、活性和安慰剂对照、五臂临床研究。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-12-01 Epub Date: 2024-01-18 DOI: 10.1177/19476035231221211
Sheena Devasia, Jinu T Joseph, Stephena P S, Seiko Koizumi, Liz Clarke, Sriraam V T, Abhilash Parameswaran Kailas, Shajil Madhavan

Objective: The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional "Wellnex" Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial (n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied.

Design: Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician's Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored.

Results: Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy.

Conclusion: The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.

目的:胶原蛋白肽的各种功能使人们对利用生物活性肽作为营养疗法来改善各种生理退行性病症产生了浓厚的兴趣。据观察,胶原蛋白肽可减轻骨关节炎的疼痛和排列困难。与传统的牛胶原蛋白肽相比,新型高功能 "Wellnex "J 型胶原蛋白肽作为膝关节骨关节炎受试者的营养补充剂,在双盲随机、积极和安慰剂对照的 5 臂临床试验(n = 100)中具有更强的改善特性。此外,还对其疗效、安全性和耐受性进行了研究:设计:5 组分别服用 2.5 克、5.0 克和 10.0 克高功能 J 型牛胶原蛋白肽、10.0 克常规胶原蛋白肽和 10.0 克安慰剂,为期 90 天。对西安大略麦克马斯特大学关节炎指数(WOMAC)评分、疼痛量表、生活质量(QoL)、医生变化印象评分(PICS)、血清 II 型胶原蛋白 C 端交联端肽(CTX-II)水平和磁共振成像骨关节炎膝关节评分(MOAKS)参数进行了监测:结果:J型2.5克胶原蛋白对WOMAC、QoL、CTX和MOAKS有明显改善,在疗效方面与传统胶原蛋白肽10克补充剂相当:该研究的两个重要结果是,J型10.0克、J型5.0克、J型2.5克和传统胶原蛋白肽10.0克补充剂被认为是对膝关节骨关节炎有益的营养保健疗法,而J型2.5克补充剂在疗效方面与传统胶原蛋白肽10.0克补充剂相当。
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引用次数: 0
Prognostic Factors for Clinical Outcome and Cartilage Regeneration after Implantation of Allogeneic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Large-Sized Cartilage Defects with Osteoarthritis. 同种异体人类脐带血间充质干细胞植入大面积软骨缺损伴骨关节炎患者后的临床结果和软骨再生的预后因素。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-12-01 Epub Date: 2024-02-16 DOI: 10.1177/19476035241231372
Se-Han Jung, Min Jung, Kwangho Chung, Sungjun Kim, Jisoo Park, Junseok Hong, Chong-Hyuk Choi, Sung-Hwan Kim

Objective: To analyze the prognostic factors for clinical outcomes and cartilage regeneration after the implantation of allogeneic human umbilical cord blood mesenchymal stem cell (hUCB-MSC) for treating large-sized cartilage defects with osteoarthritis.

Design: This study is a case-series with multiple subgroup analyses that divides the included patients into multiple subgroups based on various factors. Overall, 47 patients who underwent hUCB-MSC implantation were included. The patient-reported outcomes, magnetic resonance imaging (MRI), and second-look arthroscopy were used to assess the outcomes.

Results: Combined realignment surgery significantly correlated with clinical outcomes, particularly pain. No other factors significantly influenced the clinical outcomes in short-term period. Subgroups with large defect sizes or meniscal insufficiency showed significantly poor MRI and arthroscopy outcomes (MRI, P = 0.001, P = 0.001; arthroscopy, P = 0.032, P = 0.042). The logistic regression showed that patients with a 1 cm2 larger defect size were 1.91 times less likely to achieve favorable MRI outcomes (P = 0.017; odds ratio [OR], 1.91). Cut-off value to predict the poor outcome was >5.7 cm2 (area under the curve, 0.756). A cartilage defect size >5.7 cm2 was the major poor prognostic factor for cartilage regeneration on MRI (P = 0.010; OR, 17.46). If the postoperative alignment shifted by 1° opposite to the cartilage defect, it was 1.4 times more likely to achieve favorable MRI outcomes (P = 0.028; OR, 1.4).

Conclusion: Combining realignment surgery showed a better prognosis for pain improvement. Cartilage defect size, meniscal function, and postoperative alignment are significant prognostic factors for cartilage regeneration. A cartilage defect size >5.7 cm2 was significantly related to poor cartilage regeneration.

目的分析异体人脐血间充质干细胞(hUCB-MSC)植入治疗骨关节炎大面积软骨缺损后临床疗效和软骨再生的预后因素:本研究是一项病例系列研究,根据各种因素将纳入的患者分为多个亚组进行分析。共有47名患者接受了hUCB-间充质干细胞植入术。患者报告的结果、磁共振成像(MRI)和二次关节镜检查用于评估结果:结果:联合复位手术与临床结果,尤其是疼痛有明显相关性。结果:联合复位手术与临床疗效有明显相关性,尤其是疼痛,其他因素对短期临床疗效无明显影响。缺损面积大或半月板功能不全的亚组在核磁共振成像和关节镜检查中的疗效明显较差(核磁共振成像,P = 0.001,P = 0.001;关节镜检查,P = 0.032,P = 0.042)。逻辑回归结果显示,缺损面积大于 1 平方厘米的患者获得良好 MRI 结果的几率要低 1.91 倍(P = 0.017;几率比 [OR],1.91)。预测不良结果的临界值为 >5.7 平方厘米(曲线下面积为 0.756)。软骨缺损面积大于 5.7 平方厘米是核磁共振成像显示软骨再生不良预后的主要因素(P = 0.010;OR,17.46)。如果术后对位向软骨缺损相反方向移动1°,则获得良好磁共振成像结果的可能性增加1.4倍(P = 0.028;OR,1.4):结论:结合复位手术能更好地改善疼痛。软骨缺损大小、半月板功能和术后对位是软骨再生的重要预后因素。软骨缺损面积大于5.7平方厘米与软骨再生不良有显著关系。
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引用次数: 0
Loose Bodies Found in the Human Intra-Articular Space Showed Characteristics Similar to Endochondral Bone Formation. 在人类关节内空间发现的松散体显示出与软骨内骨形成相似的特征。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-12-01 Epub Date: 2023-12-01 DOI: 10.1177/19476035231212608
Andrea Schwab, Thomas Pap, Veit Krenn, Wolfgang Rüther, Christoph Lohmann, Jessica Bertrand

Objective: Loose bodies are free-floating tissues of cartilage and bone that can cause pain, swelling, the inability to straighten the knee, or intermittent locking of the knee. Loose bodies can arise from degenerative joint disease, flake fractures, osteochondritis dissecans, or chondromatosis. We hypothesized that loose bodies can be classified in stages with tissue characteristics similar to endochondral ossification.

Design: Loose bodies were harvested from patients undergoing joint replacement. Samples were processed for histology, gene expression analysis, and micro-computed tomography (µCT). Cartilage- and bone-related genes and proteins were selected for immunofluorescence stainings (collagen type I, II, and X, SOX9 [SRY-box transcription factor 9], and MMP13 [matrix metalloproteinase 13]) and gene expression analysis (FN [fibronectin], COL1A1, COL2A1, COL10A1, SOX9, MMP13, and aggrecan [ACAN]).

Results: Loose bodies were grouped in 4 stages: fibrous, (mineralized) cartilaginous, cartilage and bone, and bone. Hyaline-like cartilage tissue with Benninghoff arcades was present in stages 2 and 3. A transition from cartilaginous to mineralized tissue and bone trabecula was defined by an increase in COL1A1 and COL10A1 (stage 3 vs. 4: p = 0.047) positive area. Stage 4 showed typical trabecular bone tissue. The relative volume of calcified tissue (mineralized cartilage and bone tissue) decreased with stages (stages 1-2 vs. 3: p = 0.002; stage 1-2 vs. 4: p = 0.012). COL2A1 expression and stained area decreased from stages 1-2 to 4 (p = 0.010 and p = 0.004). ACAN expression decreased from stage 1-2 to stage 3 (p = 0.049) and stage 4 (p = 0.002).

Conclusion: Loose bodies show tissue characteristics similar to endochondral ossification. They are probably a relevant substrate for regenerative therapeutic interventions in joint disease.

目的:松体是自由漂浮的软骨和骨骼组织,可引起疼痛、肿胀、无法伸直膝盖或间歇性锁定膝盖。松体可由退行性关节疾病、片状骨折、夹层性骨软骨炎或软骨瘤病引起。我们假设松散体可以按照与软骨内成骨相似的组织特征进行分期分类。设计:取关节置换术患者的游离体。对样品进行组织学、基因表达分析和微计算机断层扫描(µCT)处理。选择软骨和骨相关基因和蛋白进行免疫荧光染色(ⅰ型、ⅱ型和X型胶原,SOX9 [SRY-box转录因子9]和MMP13[基质金属蛋白酶13])和基因表达分析(FN[纤维连接蛋白]、COL1A1、COL2A1、COL10A1、SOX9、MMP13和聚集蛋白[ACAN])。结果:松散体分为纤维性、(矿化)软骨、软骨与骨、骨性4个阶段。透明样软骨组织在第2期和第3期出现Benninghoff拱廊。从软骨组织向矿化组织和骨小梁过渡的定义是COL1A1和COL10A1阳性区域的增加(3期对4期:p = 0.047)。4期表现为典型的骨小梁组织。钙化组织(矿化软骨和骨组织)的相对体积随分期减少(1-2期vs. 3期:p = 0.002;1-2期vs. 4期:p = 0.012)。COL2A1的表达和染色面积从1 ~ 2期下降(p = 0.010和p = 0.004)。ACAN表达从1-2期到3期(p = 0.049)和4期(p = 0.002)下降。结论:游离体表现出与软骨内成骨相似的组织特征。它们可能是关节疾病再生治疗干预的相关底物。
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引用次数: 0
Attenuating Cartilage Degeneration in a Low Mechanical Compression Rat Model Through Intra-Articular Injections of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells. 通过关节内注射同种异体骨髓间充质干细胞减轻低机械压迫大鼠软骨退变模型。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-29 DOI: 10.1177/19476035241301291
Chia Tai, Akira Ito, Zixi Zhao, Hiroshi Kuroki, Tomoki Aoyama

Objective: Mechanical stimulation significantly contributes to posttraumatic osteoarthritis (PTOA), a condition that impedes patient recovery following intra-articular injury. Effective treatment options for compression-induced injuries are limited. Bone marrow-derived mesenchymal stem cell (BMSC) implantation has emerged as a potential therapeutic breakthrough for joint diseases. The aim of this study was to attenuate the progression of PTOA induced by cyclic loading and demonstrate the potential effectiveness of BMSCs in a rat model of low mechanical compression.

Design: Using a rat model of compression-induced articular cartilage injury, assessments were conducted 2, 4, and 8 weeks after cyclic compressive loading. The expression of matrix metallopeptidase 13, transforming growth factor-beta 3 (TGF-β3), insulin-like growth factor 1 (IGF-1), and cleaved caspase-3 was evaluated through immunohistochemistry to investigate the mechanistic aspects underlying the prevention of compression-induced injury following BMSCs treatment.

Results: Intra-articular injections of BMSCs significantly improved scores in the OARSI (Osteoarthritis Research Society International) Osteoarthritis Cartilage Histopathology Assessment System and Histological-Histochemical Grading System. This treatment showed positive outcomes in maintaining high relative cell density and reducing proteoglycan loss after cyclic compression-induced injury. The expression patterns of IGF-1 and TGF-β3 provide valuable insights into the presence and distribution of these growth factors in healthy and injured cartilage.

Conclusions: These findings highlight the efficacy of BMSCs treatment in attenuating the advancement of compression-induced injuries, albeit within a limited timeframe.

目的:机械刺激对创伤后骨关节炎(PTOA)有显著的促进作用,这是一种阻碍患者在关节内损伤后恢复的疾病。压迫性损伤的有效治疗选择是有限的。骨髓间充质干细胞(BMSC)移植已成为关节疾病治疗的潜在突破。本研究的目的是减弱由循环载荷引起的PTOA的进展,并在低机械压缩大鼠模型中证明骨髓间充质干细胞的潜在有效性。设计:采用挤压性关节软骨损伤大鼠模型,在循环压缩加载2、4和8周后进行评估。通过免疫组织化学检测基质金属肽酶13、转化生长因子-β3 (TGF-β3)、胰岛素样生长因子1 (IGF-1)和cleaved caspase-3的表达,探讨骨髓间充质干细胞治疗后预防压迫性损伤的机制。结果:关节内注射骨髓间充质干细胞可显著提高OARSI (Osteoarthritis Research Society International)骨关节炎软骨组织病理学评估系统和组织组织化学分级系统的评分。这种治疗在维持较高的相对细胞密度和减少循环压缩损伤后的蛋白多糖损失方面显示出积极的结果。IGF-1和TGF-β3的表达模式为了解这些生长因子在健康和损伤软骨中的存在和分布提供了有价值的见解。结论:这些发现强调了骨髓间充质干细胞治疗在减轻压迫性损伤进展方面的有效性,尽管在有限的时间内。
{"title":"Attenuating Cartilage Degeneration in a Low Mechanical Compression Rat Model Through Intra-Articular Injections of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells.","authors":"Chia Tai, Akira Ito, Zixi Zhao, Hiroshi Kuroki, Tomoki Aoyama","doi":"10.1177/19476035241301291","DOIUrl":"10.1177/19476035241301291","url":null,"abstract":"<p><strong>Objective: </strong>Mechanical stimulation significantly contributes to posttraumatic osteoarthritis (PTOA), a condition that impedes patient recovery following intra-articular injury. Effective treatment options for compression-induced injuries are limited. Bone marrow-derived mesenchymal stem cell (BMSC) implantation has emerged as a potential therapeutic breakthrough for joint diseases. The aim of this study was to attenuate the progression of PTOA induced by cyclic loading and demonstrate the potential effectiveness of BMSCs in a rat model of low mechanical compression.</p><p><strong>Design: </strong>Using a rat model of compression-induced articular cartilage injury, assessments were conducted 2, 4, and 8 weeks after cyclic compressive loading. The expression of matrix metallopeptidase 13, transforming growth factor-beta 3 (TGF-β3), insulin-like growth factor 1 (IGF-1), and cleaved caspase-3 was evaluated through immunohistochemistry to investigate the mechanistic aspects underlying the prevention of compression-induced injury following BMSCs treatment.</p><p><strong>Results: </strong>Intra-articular injections of BMSCs significantly improved scores in the OARSI (Osteoarthritis Research Society International) Osteoarthritis Cartilage Histopathology Assessment System and Histological-Histochemical Grading System. This treatment showed positive outcomes in maintaining high relative cell density and reducing proteoglycan loss after cyclic compression-induced injury. The expression patterns of IGF-1 and TGF-β3 provide valuable insights into the presence and distribution of these growth factors in healthy and injured cartilage.</p><p><strong>Conclusions: </strong>These findings highlight the efficacy of BMSCs treatment in attenuating the advancement of compression-induced injuries, albeit within a limited timeframe.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241301291"},"PeriodicalIF":2.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TNF-α Regulated Bidirectional Interaction Between Bone Marrow Mesenchymal Stem Cells and Articular Chondrocytes. TNF-α 调控骨髓间充质干细胞与关节软骨细胞之间的双向相互作用
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-20 DOI: 10.1177/19476035241297693
Yu Huang, Fengqiong Zuo, Jue Wu, Shaoping Wu
<p><strong>Background: </strong>Articular chondrocytes (ACs) secrete a variety of extracellular matrix components to maintain the functions of articular cartilage. Degeneration of ACs leads to the degeneration of articular cartilage and consequently to osteoarthritis. The secretion of bone marrow mesenchymal stem cells (BMSCs) is capable of protecting ACs from degeneration, and thus BMSCs are widely applied to treat osteoarthritis.</p><p><strong>Objective: </strong>This study aims to explore whether BMSCs and ACs will affect the functions of each other through their secretions in the context of osteoarthritis.</p><p><strong>Design: </strong>BMSCs and ACs isolated from rabbits were identified using flow cytometry and immunocytochemistry. Conditioned medium of BMSCs and ACs treated with 0, 5, 10, 20, and 40 ng/ml of tumor necrosis factor-alpha (TNF-α) were collected and used to treat ACs and BMSCs, respectively. The viabilities of ACs and BMSCs treated with condition medium were assessed using a Cell Count Kit-8 (CCK-8) kit. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) methods were employed to evaluate the relative expression levels of genes and proteins, as well as the cytokine concentrations in the supernatant.</p><p><strong>Results: </strong>Immunofluorescence and flow cytometry results indicated that the purity of isolated cells exceeded 95%. CCK-8 analysis showed that 6 hours of treatment with a conditioned medium did not affect the viability of BMSCs and ACs. However, treatment for 12 hours or longer significantly increased the viability of BMSCs (<i>p</i> < 0.05) and significantly decreased the viability of ACs (<i>p</i> < 0.01). RT-qPCR results demonstrated that the relative expression levels of <i>Runx2</i> (1.15-3.91), <i>Alp</i> (1.06-2.84), <i>TNF</i> (BMSCs: 0.94-2.54; ACs: 1.03-2.64), <i>IL6</i> (BMSCs: 0.98-2.78; ACs: 0.96-3.71), <i>IL17A</i> (BMSCs: 1.08-5.91; ACs: 0.90-4.20), and <i>IL10</i> (BMSCs: 0.93-2.82; ACs: 0.89-2.25) genes in conditioned medium-treated BMSCs and ACs were dose-dependently elevated (<i>p</i> < 0.001) by TNF-α treatment. Immunoblotting analysis revealed that the expression levels of RUNX2 (0.53-0.86) and ALP (0.49-0.85) proteins were also dose-dependently elevated (<i>p</i> < 0.001) by TNF-α treatment. ELISA results showed similar TNF-α dose-dependent increases (<i>p</i> < 0.001) in the supernatant concentrations of pro-inflammatory cytokines TNF-α (BMSCs: 36.90 ± 0.75 to 199.38 pg/ml; ACs: 29.76 to 293.99 pg/ml), interleukin (IL)-6 (BMSCs: 4.96-48.24 pg/ml; ACs: 6.12-38.15 pg/ml), IL-17 (BMSCs: 3.06-28.99 pg/ml; ACs: 3.08-28.51 pg/ml), as well as the anti-inflammatory cytokine IL-10 (BMSCs: 6.34-65.02 pg/ml; ACs: 5.30-34.85 pg/ml).</p><p><strong>Conclusion: </strong>Together, these results indicate a TNF-α-regulated bidirectional interaction between BMSCs and ACs, deepening our understanding of the pathogenesis of osteoa
背景:关节软骨细胞(AC)分泌多种细胞外基质成分,以维持关节软骨的功能。关节软骨细胞的退化会导致关节软骨的退化,进而引发骨关节炎。骨髓间充质干细胞(BMSCs)的分泌物能够保护关节软骨免于退化,因此骨髓间充质干细胞被广泛应用于治疗骨关节炎:本研究旨在探讨在骨关节炎的背景下,BMSCs 和 ACs 是否会通过其分泌物影响对方的功能:设计:使用流式细胞术和免疫细胞化学鉴定从兔子体内分离的BMSCs和ACs。收集经 0、5、10、20 和 40 ng/ml 肿瘤坏死因子-α(TNF-α)处理的 BMSCs 和 ACs 的条件培养基,分别用于处理 ACs 和 BMSCs。使用细胞计数试剂盒-8(CCK-8)评估用条件培养基处理的 ACs 和 BMSCs 的活力。采用逆转录-定量聚合酶链反应(RT-qPCR)、免疫印迹和酶联免疫吸附试验(ELISA)方法评估基因和蛋白质的相对表达水平以及上清液中细胞因子的浓度:免疫荧光和流式细胞术结果表明,分离细胞的纯度超过 95%。CCK-8 分析表明,用条件培养基处理 6 小时不会影响 BMSCs 和 ACs 的活力。然而,处理 12 小时或更长时间会显著提高 BMSCs 的活力(p < 0.05),显著降低 ACs 的活力(p < 0.01)。RT-qPCR 结果表明,Runx2(1.15-3.91)、Alp(1.06-2.84)、TNF(BMSCs:0.94-2.54;ACs:1.03-2.64)、IL6(BMSCs:0.98-2.78;ACs:0.96-3.71)、IL17A(BMSCs:1.经 TNF-α 处理的 BMSCs 和 ACs 条件培养基中的 IL6(BMSCs:0.98-2.78;ACs:0.96-3.71)、IL17A(BMSCs:1.08-5.91;ACs:0.90-4.20)和 IL10(BMSCs:0.93-2.82;ACs:0.89-2.25)基因呈剂量依赖性升高(p < 0.001)。免疫印迹分析显示,RUNX2(0.53-0.86)和ALP(0.49-0.85)蛋白的表达水平也因TNF-α处理而呈剂量依赖性升高(p < 0.001)。ELISA结果显示,TNF-α剂量依赖性增加(p < 0.001)的促炎细胞因子TNF-α(BMSCs:36.90 ± 0.75 至 199.38 pg/ml;ACs:29.76 至 293.99 pg/ml)、白细胞介素(IL)-6(BMSCs:4.白细胞介素(IL)-6(BMSCs:4.96-48.24 pg/ml;ACs:6.12-38.15 pg/ml)、IL-17(BMSCs:3.06-28.99 pg/ml;ACs:3.08-28.51 pg/ml)以及抗炎细胞因子IL-10(BMSCs:6.34-65.02 pg/ml;ACs:5.30-34.85 pg/ml):总之,这些结果表明 TNF-α 调节的 BMSCs 和 ACs 之间的双向相互作用,加深了我们对骨关节炎发病机制的了解,有助于骨关节炎的预防和治疗。
{"title":"TNF-α Regulated Bidirectional Interaction Between Bone Marrow Mesenchymal Stem Cells and Articular Chondrocytes.","authors":"Yu Huang, Fengqiong Zuo, Jue Wu, Shaoping Wu","doi":"10.1177/19476035241297693","DOIUrl":"10.1177/19476035241297693","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Articular chondrocytes (ACs) secrete a variety of extracellular matrix components to maintain the functions of articular cartilage. Degeneration of ACs leads to the degeneration of articular cartilage and consequently to osteoarthritis. The secretion of bone marrow mesenchymal stem cells (BMSCs) is capable of protecting ACs from degeneration, and thus BMSCs are widely applied to treat osteoarthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to explore whether BMSCs and ACs will affect the functions of each other through their secretions in the context of osteoarthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;BMSCs and ACs isolated from rabbits were identified using flow cytometry and immunocytochemistry. Conditioned medium of BMSCs and ACs treated with 0, 5, 10, 20, and 40 ng/ml of tumor necrosis factor-alpha (TNF-α) were collected and used to treat ACs and BMSCs, respectively. The viabilities of ACs and BMSCs treated with condition medium were assessed using a Cell Count Kit-8 (CCK-8) kit. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) methods were employed to evaluate the relative expression levels of genes and proteins, as well as the cytokine concentrations in the supernatant.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Immunofluorescence and flow cytometry results indicated that the purity of isolated cells exceeded 95%. CCK-8 analysis showed that 6 hours of treatment with a conditioned medium did not affect the viability of BMSCs and ACs. However, treatment for 12 hours or longer significantly increased the viability of BMSCs (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) and significantly decreased the viability of ACs (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). RT-qPCR results demonstrated that the relative expression levels of &lt;i&gt;Runx2&lt;/i&gt; (1.15-3.91), &lt;i&gt;Alp&lt;/i&gt; (1.06-2.84), &lt;i&gt;TNF&lt;/i&gt; (BMSCs: 0.94-2.54; ACs: 1.03-2.64), &lt;i&gt;IL6&lt;/i&gt; (BMSCs: 0.98-2.78; ACs: 0.96-3.71), &lt;i&gt;IL17A&lt;/i&gt; (BMSCs: 1.08-5.91; ACs: 0.90-4.20), and &lt;i&gt;IL10&lt;/i&gt; (BMSCs: 0.93-2.82; ACs: 0.89-2.25) genes in conditioned medium-treated BMSCs and ACs were dose-dependently elevated (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) by TNF-α treatment. Immunoblotting analysis revealed that the expression levels of RUNX2 (0.53-0.86) and ALP (0.49-0.85) proteins were also dose-dependently elevated (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) by TNF-α treatment. ELISA results showed similar TNF-α dose-dependent increases (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) in the supernatant concentrations of pro-inflammatory cytokines TNF-α (BMSCs: 36.90 ± 0.75 to 199.38 pg/ml; ACs: 29.76 to 293.99 pg/ml), interleukin (IL)-6 (BMSCs: 4.96-48.24 pg/ml; ACs: 6.12-38.15 pg/ml), IL-17 (BMSCs: 3.06-28.99 pg/ml; ACs: 3.08-28.51 pg/ml), as well as the anti-inflammatory cytokine IL-10 (BMSCs: 6.34-65.02 pg/ml; ACs: 5.30-34.85 pg/ml).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Together, these results indicate a TNF-α-regulated bidirectional interaction between BMSCs and ACs, deepening our understanding of the pathogenesis of osteoa","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241297693"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Meniscus Injury Induces Patellofemoral Osteoarthritis Development Mediated by Synovitis and Gait Kinematics: A Preclinical Study. 半月板损伤通过滑膜炎和步态运动学诱发髌骨骨关节炎的发展:临床前研究
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-20 DOI: 10.1177/19476035241299769
Akihiro Nakahata, Akira Ito, Ryo Nakahara, Hiroshi Kuroki

Objective: To investigate whether meniscal injury leads to the development of patellofemoral (PF) osteoarthritis (PFOA) and to explore how synovitis and gait kinematics mediate this relationship.

Methods: Fifty-four male Wistar rats (12 weeks old) were randomly assigned to the control, sham, or destabilized medial meniscus (DMM) groups. The rats were subjected to gait analysis to assess the kinematic changes at 2, 4, and 8 weeks postoperatively. Subsequently, the rats were euthanized, and their right knees were harvested for histological analysis.

Results: The Osteoarthritis Research Society International (OARSI) and modified Mankin (MM) scores in the DMM group were significantly higher than those in the control and sham groups at week 2 and significantly higher than those in the control group at week 4. The OARSI and MM scores in the sham group were significantly higher than those in the control group at weeks 2 and 4. The association between the DMM and OARSI scores was significantly mediated by the synovitis score and knee flexion angle at foot contact (proportion mediated: 58% and 10%, respectively). The association between the sham and OARSI scores was significantly mediated by the synovitis score and knee flexion angle (proportion mediated: 24% and 24%, respectively).

Conclusions: DMM surgery induced articular cartilage damage in the PF joint. Synovitis and the knee flexion angle significantly mediated the association between DMM or sham surgery and PFOA development.

目的研究半月板损伤是否会导致髌股骨(PF)骨关节炎(PFOA)的发生,并探讨滑膜炎和步态运动学如何介导这种关系:54只雄性Wistar大鼠(12周大)被随机分配到对照组、假组或内侧半月板失稳(DMM)组。对大鼠进行步态分析,以评估其术后 2、4 和 8 周的运动学变化。随后,对大鼠实施安乐死,并采集其右膝关节进行组织学分析:结果:第 2 周时,DMM 组的国际骨关节炎研究学会(OARSI)和改良 Mankin(MM)评分明显高于对照组和假体组,第 4 周时又明显高于对照组。在第 2 周和第 4 周,假体组的 OARSI 和 MM 分数明显高于对照组。滑膜炎评分和足部接触时的膝关节屈曲角度对DMM和OARSI评分之间的关联有明显的中介作用(中介作用比例分别为58%和10%)。滑膜炎评分和膝关节屈曲角对假关节炎评分和OARSI评分之间的关联有明显的中介作用(中介作用比例分别为24%和24%):结论:DMM手术会导致PF关节软骨损伤。结论:DMM手术会导致PF关节软骨损伤,滑膜炎和膝关节屈曲角度对DMM或假手术与PFOA发展之间的关系有明显的中介作用。
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引用次数: 0
Anterior Cruciate Ligament Reconstruction and Concomitant Focal Cartilage Lesions: A Systematic Review and Meta-Analysis of Prognosis after Surgical Treatment. 前十字韧带重建与并发病灶性软骨损伤:手术治疗后预后的系统回顾和 Meta 分析。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-20 DOI: 10.1177/19476035241292719
Diko Jevremovic, Asbjørn Årøen, Owen Matthew Truscott Thomas, Hilde Moseby Berge, Ahsan Ayub Khan, Svend Ulstein

Objective: To synthesize available evidence on the impact of concomitant focal cartilage lesions and their surgical treatment on clinical outcomes in the setting of anterior cruciate ligament (ACL)-reconstruction at short (6-36 months) and midterm (3-8 years) follow-up.

Design: Original level 1 or 2 studies comparing any patient-reported or objective outcomes in ACL-reconstructed patients (1) with and without concomitant focal cartilage lesion(s) or (2) after any type of cartilage surgical treatment were considered for inclusion. Systematic searches were conducted in MEDLINE via Ovid, Cochrane Library, EMBASE via OvidSP, and Web of Science.

Results: In meta-analysis performed across 6 studies (n=8,789 patients), we discovered with very low certainty, the correlation of concomitant any-thickness cartilage lesions and worse Patient-Reported Outcome Measure scores (PROMS) at cumulative short to mid, (pooled standardized mean difference (psmd) = -0.36; 95% confidence interval (CI) -0.62 to -0.10), short (psmd = -0.43; 95% CI = -0.94 to 0.08), and midterm (psmd = -0.22; 95% CI -0.43 to 0.00). Full-thickness lesions predicted worse PROMS with moderate certainty at cumulative short-midterm (psmd = -0.32; 95% CI = -0.41 to -0.23) and low certainty at both short (psmd = -0.45; 95% CI -0.83 to -0.07) and midterm (psmd = -0.30; 95% CI -0.38 to -0.22). In 4 studies for each outcome, mixed results were reported on osteoarthritis (OA) and reoperation rates.

Conclusions: As the main finding, concomitant full-thickness cartilage lesions in ACL-reconstructed patients are a predictor of worse PROMS in the cumulative short to midterm. Correlations of any-thickness lesions or different cartilage treatments with short- or midterm PROMS, OA, or reoperation rates were either with very low certainty, unmeasured, or with mixed results.

目的综合现有证据,说明在前交叉韧带(ACL)重建的短期(6-36 个月)和中期(3-8 年)随访中,伴随病灶性软骨损伤及其手术治疗对临床疗效的影响:设计:对下列情况下前交叉韧带重建患者的患者报告结果或客观结果进行比较的原创1级或2级研究均可纳入考虑范围:(1)伴有或不伴有病灶性软骨损伤;或(2)经过任何类型的软骨手术治疗。通过 Ovid 在 MEDLINE、Cochrane Library、OvidSP 的 EMBASE 和 Web of Science 进行了系统检索:在对 6 项研究(n=8789 名患者)进行的荟萃分析中,我们以极低的确定性发现,同时存在任何厚度的软骨病变与累积中短期患者报告结果测量评分(PROMS)的相关性较差(汇总标准化平均差(psmd)=-0.36; 95% 置信区间 (CI) -0.62 to -0.10)、短期(psmd = -0.43; 95% CI = -0.94 to 0.08)和中期(psmd = -0.22; 95% CI -0.43 to 0.00)。全厚度病变可预测较差的PROMS,中度确定性为中短期累积(psmd = -0.32;95% CI = -0.41至-0.23),低确定性为短期(psmd = -0.45;95% CI -0.83至-0.07)和中期(psmd = -0.30;95% CI -0.38至-0.22)。在4项研究的每项结果中,关于骨关节炎(OA)和再手术率的报告结果不一:结论:作为主要发现,前交叉韧带重建患者并发全厚软骨损伤是中短期累积PROMS较差的预测因素。任何厚度的病变或不同的软骨治疗方法与短期或中期PROMS、OA或再手术率之间的相关性要么确定性很低、要么无法测量、要么结果不一。
{"title":"Anterior Cruciate Ligament Reconstruction and Concomitant Focal Cartilage Lesions: A Systematic Review and Meta-Analysis of Prognosis after Surgical Treatment.","authors":"Diko Jevremovic, Asbjørn Årøen, Owen Matthew Truscott Thomas, Hilde Moseby Berge, Ahsan Ayub Khan, Svend Ulstein","doi":"10.1177/19476035241292719","DOIUrl":"10.1177/19476035241292719","url":null,"abstract":"<p><strong>Objective: </strong>To synthesize available evidence on the impact of concomitant focal cartilage lesions and their surgical treatment on clinical outcomes in the setting of anterior cruciate ligament (ACL)-reconstruction at short (6-36 months) and midterm (3-8 years) follow-up.</p><p><strong>Design: </strong>Original level 1 or 2 studies comparing any patient-reported or objective outcomes in ACL-reconstructed patients (1) with and without concomitant focal cartilage lesion(s) or (2) after any type of cartilage surgical treatment were considered for inclusion. Systematic searches were conducted in MEDLINE via Ovid, Cochrane Library, EMBASE via OvidSP, and Web of Science.</p><p><strong>Results: </strong>In meta-analysis performed across 6 studies (n=8,789 patients), we discovered with very low certainty, the correlation of concomitant any-thickness cartilage lesions and worse Patient-Reported Outcome Measure scores (PROMS) at cumulative short to mid, (pooled standardized mean difference (psmd) = -0.36; 95% confidence interval (CI) -0.62 to -0.10), short (psmd = -0.43; 95% CI = -0.94 to 0.08), and midterm (psmd = -0.22; 95% CI -0.43 to 0.00). Full-thickness lesions predicted worse PROMS with moderate certainty at cumulative short-midterm (psmd = -0.32; 95% CI = -0.41 to -0.23) and low certainty at both short (psmd = -0.45; 95% CI -0.83 to -0.07) and midterm (psmd = -0.30; 95% CI -0.38 to -0.22). In 4 studies for each outcome, mixed results were reported on osteoarthritis (OA) and reoperation rates.</p><p><strong>Conclusions: </strong>As the main finding, concomitant full-thickness cartilage lesions in ACL-reconstructed patients are a predictor of worse PROMS in the cumulative short to midterm. Correlations of any-thickness lesions or different cartilage treatments with short- or midterm PROMS, OA, or reoperation rates were either with very low certainty, unmeasured, or with mixed results.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241292719"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EUROVISCO Consensus Guidelines for the Use of Hyaluronic Acid Viscosupplementation in Knee Osteoarthritis Based on Patient Characteristics. 根据患者特征制定的关于在膝关节骨性关节炎中使用透明质酸粘液补充剂的 EUROVISCO 共识指南。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-20 DOI: 10.1177/19476035241271970
Thierry Conrozier, Raghu Raman, Demirhan Diraçoglu, Jordi Montfort, Hervé Bard, Dominique Baron, Belarmino Goncalves, Pascal Richette, Alberto Migliore, Xavier Chevalier, Mats Brittberg, Yves Henrotin

Objectives: Viscosupplementation with hyaluronic acid (HA) is a commonly used intra-articular treatment for osteoarthritis (OA). We performed a Delphi consensus process to formulate guidelines for the use of intra-articular hyaluronic acid (IAHA) knee injection according to the patient's characteristics.

Methods: The EUROVISCO group consists of 12 members who had expertise in clinical and/or research in the field of OA and IAHA treatment. This group drafted issues through an iterative process and subsequently voted according to a Delphi process on their level of agreement (LoA) on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. The strength of the recommendation (SOR) was classified as strong if the median agreement score was ≥8. The level of consensus (LOC) was also obtained. The level of evidence was given for each recommendation.

Results: A total of 34 statements were evaluated by the expert group. A unanimous or high LoA was obtained in 16. IAHA can be considered irrespective of the age in patients with symptomatic knee OA. It can be used in patients with diabetes and/or moderate to severe obesity. It can also be used in knee OA patients with a history of gout, meniscocalcinosis and with mild-to-moderate varus/valgus malalignment. The group recommended against the use of VS in pregnant women and in OA flare.

Conclusion: In summary, the working group provided strong recommendations for the use of IAHA injection that will facilitate individualized treatment decision algorithms in the management of knee OA.

目的:用透明质酸(HA)补充粘液是骨关节炎(OA)常用的关节内治疗方法。我们通过德尔菲共识程序,根据患者的特点制定了膝关节内注射透明质酸(IAHA)的使用指南:EUROVISCO小组由12名成员组成,他们在OA和IAHA治疗领域拥有临床和/或研究方面的专业知识。该小组通过迭代程序起草问题,随后根据德尔菲程序就这些建议的一致程度(LoA)进行投票。得分汇总后得出每项建议的中位同意度得分。如果协议得分中值≥8 分,则该建议的强度(SOR)被归类为强。此外,还获得了共识水平(LOC)。每条建议都给出了证据等级:专家组共评估了 34 项建议。结果:专家组共评估了 34 项声明,其中 16 项获得了一致或高度的 LoA。对于有症状的膝关节 OA 患者,无论年龄大小,均可考虑使用 IAHA。糖尿病和/或中度至重度肥胖患者也可使用。有痛风病史、半月板钙化症和轻度至中度膝关节内翻/外翻错位的膝关节OA患者也可使用。工作组建议孕妇和 OA 复发患者不要使用 VS:总之,工作组为使用 IAHA 注射提供了强有力的建议,这将有助于在膝关节 OA 的治疗中采用个体化治疗决策算法。
{"title":"EUROVISCO Consensus Guidelines for the Use of Hyaluronic Acid Viscosupplementation in Knee Osteoarthritis Based on Patient Characteristics.","authors":"Thierry Conrozier, Raghu Raman, Demirhan Diraçoglu, Jordi Montfort, Hervé Bard, Dominique Baron, Belarmino Goncalves, Pascal Richette, Alberto Migliore, Xavier Chevalier, Mats Brittberg, Yves Henrotin","doi":"10.1177/19476035241271970","DOIUrl":"10.1177/19476035241271970","url":null,"abstract":"<p><strong>Objectives: </strong>Viscosupplementation with hyaluronic acid (HA) is a commonly used intra-articular treatment for osteoarthritis (OA). We performed a Delphi consensus process to formulate guidelines for the use of intra-articular hyaluronic acid (IAHA) knee injection according to the patient's characteristics.</p><p><strong>Methods: </strong>The EUROVISCO group consists of 12 members who had expertise in clinical and/or research in the field of OA and IAHA treatment. This group drafted issues through an iterative process and subsequently voted according to a Delphi process on their level of agreement (LoA) on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. The strength of the recommendation (SOR) was classified as strong if the median agreement score was ≥8. The level of consensus (LOC) was also obtained. The level of evidence was given for each recommendation.</p><p><strong>Results: </strong>A total of 34 statements were evaluated by the expert group. A unanimous or high LoA was obtained in 16. IAHA can be considered irrespective of the age in patients with symptomatic knee OA. It can be used in patients with diabetes and/or moderate to severe obesity. It can also be used in knee OA patients with a history of gout, meniscocalcinosis and with mild-to-moderate varus/valgus malalignment. The group recommended against the use of VS in pregnant women and in OA flare.</p><p><strong>Conclusion: </strong>In summary, the working group provided strong recommendations for the use of IAHA injection that will facilitate individualized treatment decision algorithms in the management of knee OA.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241271970"},"PeriodicalIF":2.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regression to the Mean: Statistical Bias Can Mislead Interpretation in Cartilage and Osteoarthritis Clinics and Research. 回归均值:统计偏差会误导《软骨和骨关节炎临床与研究》的解释。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-11 DOI: 10.1177/19476035241293048
Kaj S Emanuel, Jari Dahmen, Inger N Sierevelt, Mats Brittberg, Gino M M J Kerkhoffs
{"title":"Regression to the Mean: Statistical Bias Can Mislead Interpretation in Cartilage and Osteoarthritis Clinics and Research.","authors":"Kaj S Emanuel, Jari Dahmen, Inger N Sierevelt, Mats Brittberg, Gino M M J Kerkhoffs","doi":"10.1177/19476035241293048","DOIUrl":"10.1177/19476035241293048","url":null,"abstract":"","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241293048"},"PeriodicalIF":2.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intra-Articular Injection of Human Umbilical Cord-Derived Mesenchymal Stromal Cells Reduces Radiographic Osteoarthritis in an Ovine Model. 脐带间充质干细胞的关节内注射可减轻绵羊模型的放射性骨关节炎。
IF 2.7 4区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-03 DOI: 10.1177/19476035241287832
Jade Perry, Claire Mennan, Paul Cool, Helen S McCarthy, Karin Newell, Timothy Hopkins, Charlotte Hulme, Karina T Wright, Frances M D Henson, Sally Roberts

Objective: To determine if mesenchymal stromal cells (MSCs) derived from human umbilical cords (hUC) could reduce degeneration developing when injected into the knee of a large animal model of osteoarthritis (OA).

Design: Ten million culture-expanded UC-MSCs (pooled from 3 human donors) were injected in 50 μL of tissue culture medium into the left stifle joints of 7 sheep whose medial meniscus was transected 4 weeks previously. Seven other sheep had only 50 μL of medium injected as the no treatment "control" group. After 8 weeks the sheep underwent euthanasia, the joints were excised and examined macroscopically, via x-ray and magnetic resonance imaging (MRI), both via histology for degenerative and inflammatory changes and immunohistochemically to identify any human cells within the joint tissues. Activity monitoring both before meniscus transection and euthanasia was also undertaken.

Results: There was a significant reduction in the Kellgren-Lawrence x-ray score for joints injected with hUC-MSCs compared with the control joints. Likewise, macroscopic, MRI, synovitis and OARSI histology scores were all lower (better) in the joints injected with hUC-MSCs than in the control arm, but not significantly. Activity levels and synovitis scores were similar in both groups of animals.

Conclusions: hUC-MSCs appear to modify and reduce the development of osteoarthritic changes in the ovine stifle joint after meniscal destabilization, an injury which commonly leads to OA in humans. These results are encouraging for the potential benefit of culture expanded UC-MSCs as an allogeneic cell therapy in patients who may have early OA following a meniscal injury of the knee.

目的确定将源自人脐带(hUC)的间充质基质细胞(MSCs)注射到骨关节炎(OA)大型动物模型的膝关节中是否能减少退化的发生:设计:将1000万个培养扩增的UC-间充质干细胞(汇集自3名人类供体)以50微升组织培养基的形式注射到7只绵羊的左跗关节中,这些绵羊在4周前曾被横断内侧半月板。另外 7 只羊只注射了 50 μL 培养基,作为无治疗 "对照 "组。8 周后,绵羊被安乐死,关节被切除,并通过 X 射线和磁共振成像(MRI)进行宏观检查,通过组织学检查退化和炎症变化,并通过免疫组化鉴定关节组织中的人体细胞。此外,还对半月板切除和安乐死前的活动进行了监测:结果:与对照组相比,注射了 hUC 间充质干细胞的关节的 Kellgren-Lawrence X 光评分明显降低。同样,注射了hUC-间充质干细胞的关节的宏观、核磁共振成像、滑膜炎和OARSI组织学评分均低于(优于)对照组,但差异不明显。结论:hUC-间充质干细胞似乎能改变和减少半月板脱位后绵羊跗关节骨关节炎病变的发展,这种损伤通常会导致人类出现 OA。这些结果令人鼓舞,对于膝关节半月板损伤后可能出现早期 OA 的患者来说,培养扩增的 UC-间充质干细胞作为一种异体细胞疗法具有潜在的益处。
{"title":"Intra-Articular Injection of Human Umbilical Cord-Derived Mesenchymal Stromal Cells Reduces Radiographic Osteoarthritis in an Ovine Model.","authors":"Jade Perry, Claire Mennan, Paul Cool, Helen S McCarthy, Karin Newell, Timothy Hopkins, Charlotte Hulme, Karina T Wright, Frances M D Henson, Sally Roberts","doi":"10.1177/19476035241287832","DOIUrl":"10.1177/19476035241287832","url":null,"abstract":"<p><strong>Objective: </strong>To determine if mesenchymal stromal cells (MSCs) derived from human umbilical cords (hUC) could reduce degeneration developing when injected into the knee of a large animal model of osteoarthritis (OA).</p><p><strong>Design: </strong>Ten million culture-expanded UC-MSCs (pooled from 3 human donors) were injected in 50 μL of tissue culture medium into the left stifle joints of 7 sheep whose medial meniscus was transected 4 weeks previously. Seven other sheep had only 50 μL of medium injected as the no treatment \"control\" group. After 8 weeks the sheep underwent euthanasia, the joints were excised and examined macroscopically, via x-ray and magnetic resonance imaging (MRI), both via histology for degenerative and inflammatory changes and immunohistochemically to identify any human cells within the joint tissues. Activity monitoring both before meniscus transection and euthanasia was also undertaken.</p><p><strong>Results: </strong>There was a significant reduction in the Kellgren-Lawrence x-ray score for joints injected with hUC-MSCs compared with the control joints. Likewise, macroscopic, MRI, synovitis and OARSI histology scores were all lower (better) in the joints injected with hUC-MSCs than in the control arm, but not significantly. Activity levels and synovitis scores were similar in both groups of animals.</p><p><strong>Conclusions: </strong>hUC-MSCs appear to modify and reduce the development of osteoarthritic changes in the ovine stifle joint after meniscal destabilization, an injury which commonly leads to OA in humans. These results are encouraging for the potential benefit of culture expanded UC-MSCs as an allogeneic cell therapy in patients who may have early OA following a meniscal injury of the knee.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241287832"},"PeriodicalIF":2.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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