CARTILAGEPub Date : 2024-12-09DOI: 10.1177/19476035241304526
Mustafa Dinç, Ömer Cevdet Soydemir
{"title":"Exploring the Efficacy of Joint Lavage in Knee Osteoarthritis: A Focus on Cytokines, Degrading Enzymes, and Oxidative Stress.","authors":"Mustafa Dinç, Ömer Cevdet Soydemir","doi":"10.1177/19476035241304526","DOIUrl":"10.1177/19476035241304526","url":null,"abstract":"<p><strong>Purpose/aim: </strong>This study aimed to assess the effectiveness of joint lavage in managing knee osteoarthritis (OA) by evaluating its effect on pain relief, inflammatory markers, cartilage-degrading enzymes, and oxidative stress.</p><p><strong>Methods: </strong>Seventy patients with Kellgren-Lawrence grade 2 or 3 knee OA were selected for this single-center study. Joint lavage was performed, and pain and function were measured using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at baseline and 24 weeks postintervention. Synovial fluid samples were collected at baseline, before lavage, and 24 weeks postintervention. Samples were stored at -80°C and analyzed in batches to minimize variability. At the time of analysis, the samples were thawed and evaluated for levels of proinflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), matrix metalloproteinase-3 (MMP-3), and total oxidant status (TOS), and oxidative stress index (OSI).</p><p><strong>Results: </strong>Postintervention, VAS, and WOMAC scores significantly decreased (<i>P</i> < 0.001), with 100% achieving the minimal clinically important difference (MCID). Patient acceptable symptom state (PASS) rates varied: VAS (80%), WOMAC pain (50%), function (81.4%), and total (84.3%). Cytokine levels (IL-1β, IL-6, TNF-α) and MMP-3 significantly decreased (<i>P</i> < 0.001), along with TOS and OSI. Baseline TNF-α, IL-6, and IL-1β levels were significantly correlated with improvements in VAS and WOMAC scores. Moderate correlations were observed between reductions in IL-6/TNF-α and improvements in VAS/WOMAC. No significant associations were found between confounders and outcomes.</p><p><strong>Conclusions: </strong>Joint lavage resulted in marked pain relief and functional improvement while significantly reducing inflammatory markers, cartilage-degrading enzymes, and oxidative stress.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241304526"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799621","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}
{"title":"Relationship Between the Subchondral Trabecular Bone Microstructure in the Hip Joint and Pain in Patients with Hip Osteoarthritis.","authors":"Hiroki Kaneta, Takeshi Shoji, Yuichi Kato, Hideki Shozen, Shinichi Ueki, Hiroyuki Morita, Yosuke Kozuma, Nobuo Adachi","doi":"10.1177/19476035241302978","DOIUrl":"10.1177/19476035241302978","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the relationship between clinical findings and the trabecular microstructure of the subchondral bone in patients with hip osteoarthritis (OA) due to developmental dysplasia of the hip (DDH) using multidetector row computed tomography (MDCT).</p><p><strong>Design: </strong>A total of 63 patients (69 hips) with OA due to DDH were retrospectively reviewed, with 12 healthy controls being included for comparison. Clinical evaluation was performed using the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ). The trabecular bone microstructure was analyzed using MDCT. Regions of interest in the subchondral trabecular bones of the acetabulum and femoral head were defined in the coronal view, and various trabecular microstructural parameters were evaluated.</p><p><strong>Results: </strong>Bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) exhibited a significant positive correlation with the OA stage, whereas trabecular separation (Tb.Sp) showed a negative correlation. In addition, BV/TV and Tb.Th were negatively correlated with the JHEQ total and pain scores, whereas Tb.Sp was positively correlated with the pain score in all regions.</p><p><strong>Conclusions: </strong>This is the first study to evaluate the bone microstructure and its relationship with clinical findings in patients with hip OA due to DDH. Our findings suggest that as OA progresses, osteosclerotic changes increase in the acetabulum and femoral head; these changes are associated with worsening clinical symptoms, particularly pain. Targeting the subchondral bone may emerge as a novel treatment strategy for patients with OA due to DDH; nevertheless, further comprehensive studies are required.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241302978"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799375","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}
CARTILAGEPub Date : 2024-12-09DOI: 10.1177/19476035241304308
James J Butler, John F Dankert, Laura E Keller, Mohammad T Azam, Jari Dahmen, Gino M M J Kerkhoffs, John G Kennedy
{"title":"Assessment of the Monocyte Subpopulations and M1/M2 Macrophage Ratio in Concentrated Bone Marrow Aspirate.","authors":"James J Butler, John F Dankert, Laura E Keller, Mohammad T Azam, Jari Dahmen, Gino M M J Kerkhoffs, John G Kennedy","doi":"10.1177/19476035241304308","DOIUrl":"10.1177/19476035241304308","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to determine the M1/M2 macrophage ratio in concentrated bone marrow aspirate (cBMA) in patients undergoing surgical intervention augmented with cBMA for osteochondral lesions of the talus (OLTs).</p><p><strong>Design: </strong>Samples of peripheral blood (PB), bone marrow aspirate (BMA), and cBMA were collected during the procedure. The samples were analyzed by automated cell counting and multicolor fluorescence-activated cell sorting with specific antibodies recognizing monocytes (CD14+ CD16+) and the M1 (CD86+) and M2 (CD163+CD206+) populations within that monocyte population. Cytokine concentrations within the samples were evaluated with enzyme-linked immunosorbent assay (ELISA). The composition of cBMA was compared between 2 commercially available BMA concentration systems.</p><p><strong>Results: </strong>Thirty-eight patients with a mean age of 43.2 ± 10.1 years old undergoing a surgical procedure for the treatment of OLTs involving the use of cBMA were included. cBMA had a mean fold increase of 4.7 for all white blood cells, 6.1 for monocytes, 7.9 for lymphocytes, 2.4 for neutrophils, and 9.6 for platelets when compared to BMA. The mean M1/M2 ratio for PB, BMA, and cBMA was 15.2 ± 12.0, 20.8 ± 13.3, and 22.1 ± 16.0, respectively. There was a statistically significant higher concentration of interleukin-1 receptor antagonist (IL-1Ra) in the cBMA sample (8243.3 ± 14,837.4 pg/mL) compared to both BMA (3143.0 ± 2218.5 pg/mL) and PB (1847.5 ± 1520.4 pg/mL) samples. The IL-1Ra/IL-1β ratio for PB, BMA, and cBMA was 790.6 ± 581.9, 764.7 ± 675.2, and 235.7 ± 192.1, respectively. There was no difference in the cBMA M1/M2 ratio (19.0 ± 11.1 vs 24.0 ± 18.3) between the Magellan (Isto Biologics, Hopkinton, Massachusetts) and Angel systems (Arthrex Inc, Naples, Florida).</p><p><strong>Conclusion: </strong>This prospective study found that the M1/M2 ratio in cBMA was 22.1 ± 16.0, with significant patient to patient variation observed. Overall, there was no statistically significant difference in the M1/M2 ratio across PB, BMA, and cBMA samples. This is the first study to characterize the macrophage subpopulation within cBMA, which may have significant clinical implications in future studies.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241304308"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799619","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}
CARTILAGEPub Date : 2024-12-05DOI: 10.1177/19476035241292322
Yogen Thever, Michael Shen Xuanrong, Toh Rong Chuin, Hamid Rahmatullah Bin Abd Razak
{"title":"Comparison of Early-Stage Knee Osteoarthritis Induced by Medial Meniscus Tear Versus Tibial Osteotomy in the Rat Model.","authors":"Yogen Thever, Michael Shen Xuanrong, Toh Rong Chuin, Hamid Rahmatullah Bin Abd Razak","doi":"10.1177/19476035241292322","DOIUrl":"10.1177/19476035241292322","url":null,"abstract":"<p><strong>Objective: </strong>Medial meniscus tear (MMT) is a common method to induce osteoarthritis in rats, but mimics secondary osteoarthritis. A novel method of carrying out a medial wedge closing tibial osteotomy (TO) has been recently developed to induce primary osteoarthritis. This study aims to validate it, compared to MMT.</p><p><strong>Methods: </strong>Twenty rats were divided equally into 2 groups. Outcome measures such as histology graded according to Osteoarthritis Research Society International (OARSI) guidelines and computed tomography (CT) scans were analyzed at 6 weeks post-operatively. Observational gait analysis and serum biomarkers such as C-terminal cross-linked telopeptides of type II collagen (CTX-II) and <i>interleukin</i>-1 beta (IL-1β) were collected at 2-weekly intervals up to 6 weeks post-operatively.</p><p><strong>Results: </strong>Serum CTX-II and IL-1β levels did not reveal a statistically significant difference across all time points between the 2 groups. CT grading was significantly more severe (2.80 ± 1.10 vs 1.40 ± 0.548, <i>P</i> = 0.0389) in the MMT group compared to the TO group. In addition, histological gradings such as calcified cartilage score (2.10 ± 1.91 vs 0.00 ± 0.00, <i>P</i> < 0.01) and cartilage degeneration score (4.80 ± 5.18 vs 0.00 ± 0.00, <i>P</i> < 0.01) revealed significantly more severe osteoarthritis in the MMT compared to TO group. Synovial membrane score did not reveal a statistically significant difference (1.10 ± 0.994 vs 1.00 ± 0.00, <i>P</i> = 1.00).</p><p><strong>Conclusion: </strong>TO is a novel method in inducing primary osteoarthritis in the rat model compared to MMT between the 6 and 12 weeks' time frame.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"19476035241292322"},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779432","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}
CARTILAGEPub Date : 2024-12-01Epub Date: 2024-03-04DOI: 10.1177/19476035231226418
T Struik, M P Jansen, R G P Lafeber, F P J G Lafeber, S C Mastbergen
{"title":"Comparison of Clinical Efficacy and Mechanical Characteristics of Two Knee Distraction Devices With Relevance for Clinical Practice.","authors":"T Struik, M P Jansen, R G P Lafeber, F P J G Lafeber, S C Mastbergen","doi":"10.1177/19476035231226418","DOIUrl":"10.1177/19476035231226418","url":null,"abstract":"<p><strong>Objective: </strong>Distraction treatment for severe osteoarthritis below the age of 65 successfully postpones arthroplasty. Most patients have been treated with a general external fixator or a device specifically intended for knee distraction. This study compares clinical efficacy of both devices in retrospect and their mechanical characteristics.</p><p><strong>Design: </strong>Clinical efficacy 2 years posttreatment was compared using retrospective data from patients with severe knee osteoarthritis treated with knee distraction; 63 with the Dynamic Monotube (Stryker GmbH, Switzerland) and 65 with the KneeReviver (ArthroSave BV, the Netherlands). Changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function, general well-being (SF-36), cartilage thickness by radiographic joint space widening, and adverse events during treatment were assessed. Axial stiffness of clinically feasible configurations was assessed by bench testing for the Dynamic Monotube triax system and the KneeReviver.</p><p><strong>Results: </strong>No differences were observed in clinical efficacy, nor in mechanical characteristics and adverse events between the two devices. Although with large variation, both showed a clinically relevant improvement. In mechanical testing, contact between articular surfaces was observed for both devices at physiological loading. Stiffness of applied configurations strongly varied and primarily depended on bone pin length.</p><p><strong>Conclusions: </strong>Patients treated with a general intended-use device or a distraction-specific device both experienced clinical and structural efficacy although with significant variation between patients. The latter may be the result of varying mechanical characteristics resulting from differences in clinical configurations of the devices and actual loading. The exact role of full/partial mechanical unloading of the joint during distraction treatment remains unclear.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"407-416"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027445","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}
CARTILAGEPub Date : 2024-12-01Epub Date: 2023-08-31DOI: 10.1177/19476035231194771
Wei Xu, Juan Wang, Lin Cui, Chen Huang, Ning Xia, Meiming Xie, Da Liu, Dongfa Liao
{"title":"Il-1β Promotes Superficial Zone Cells Senescence in Articular Cartilage by Inhibiting Autophagy.","authors":"Wei Xu, Juan Wang, Lin Cui, Chen Huang, Ning Xia, Meiming Xie, Da Liu, Dongfa Liao","doi":"10.1177/19476035231194771","DOIUrl":"10.1177/19476035231194771","url":null,"abstract":"<p><strong>Objective: </strong>The superficial zone cells in articular cartilage (SFZCs) have been identified as stem/progenitor chondrocytes and promoted cell self-renewal in the osteoarthritis (OA). Several studies emphasized the involvement of senescence and autophagy in OA. Interleukin-1β (IL-1β) is one of the main inflammatory mediators of OA, and whether it induces senescence and autophagy in SFZCs remains unclear. The present study aimed to investigate autophagy flux, mitochondrial function, and intracellular reactive oxygen species (ROS) that resulted in senescence in SFZCs induced by IL-1β.</p><p><strong>Methods: </strong>Using western blotting, reverse transcription-quantitative PCR, immunofluorescence, intracellular ROS detection, mitochondrial staining, and determination of mitochondrial membrane potential, we tested senescence and autophagy markers in SFZCs induced by IL-1β <i>in vitro</i>. The consequences of mitochondrial function and ROS were also studied with IL-1β-induced senescence.</p><p><strong>Results: </strong>IL-1β treatment decreased SFZC proliferation, induced SFZC senescence, and reduced SFZCs' chondrogenic differentiation capacity. Moreover, IL-1β impaired autophagy flux, and the autophagy activator, rapamycin, attenuated the senescence of SFZCs. IL-1β-induced autophagy defect resulted in mitochondrial dysfunction and overproduction of ROS, and autophagy activation notably protected against mitochondrial dysfunction and reduced the levels of ROS. Moreover, antioxidant N-acetylcysteine reversed the senescence of IL-1β in SFZCs.</p><p><strong>Conclusion: </strong>IL-1β promotes autophagy impairment and subsequently results in dysfunctional mitochondria and overproduction of ROS, which finally causes SFZC senescence.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"428-439"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119355","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}
CARTILAGEPub Date : 2024-12-01Epub Date: 2023-09-01DOI: 10.1177/19476035231193090
Nada Abughazaleh, Kevin Boldt, Jaqueline Lourdes Rios, Stela Marcia Mattiello, Kelsey H Collins, Ruth-Anne Seerattan, Walter Herzog
{"title":"Aerobic and Resistance Training Attenuate Differently Knee Joint Damage Caused by a High-Fat-High-Sucrose Diet in a Rat Model.","authors":"Nada Abughazaleh, Kevin Boldt, Jaqueline Lourdes Rios, Stela Marcia Mattiello, Kelsey H Collins, Ruth-Anne Seerattan, Walter Herzog","doi":"10.1177/19476035231193090","DOIUrl":"10.1177/19476035231193090","url":null,"abstract":"<p><strong>Objective: </strong>Obesity and associated low-level local systemic inflammation have been linked to an increased rate of developing knee osteoarthritis (OA). Aerobic exercise has been shown to protect the knee from obesity-induced joint damage. The aims of this study were to determine (1) if resistance training provides beneficial metabolic effects similar to those previously observed with aerobic training in rats consuming a high-fat/high-sucrose (HFS) diet and (2) if these metabolic effects mitigate knee OA in a diet-induced obesity model in rats.</p><p><strong>Design: </strong>Twelve-week-old Sprague-Dawley rats were randomized into 4 groups: (1) a group fed an HFS diet subjected to aerobic exercise (HFS+Aer), (2) a group fed an HFS diet subjected to resistance exercise (HFS+Res), (3) a group fed an HFS diet with no exercise (HFS+Sed), and (4) a chow-fed sedentary control group (Chow+Sed). HFS+Sed animals were heavier and had greater body fat, higher levels of triglycerides and total cholesterol, and more joint damage than Chow+Sed animals.</p><p><strong>Results: </strong>The HFS+Res group had higher body mass and body fat than Chow+Sed animals and higher OA scores than animals from the HFS+Aer group. Severe bone lesions were observed in the HFS+Sed and Chow+Sed animals at age 24 weeks, but not in the HFS+Res and HFS+Aer group animals.</p><p><strong>Conclosion: </strong>In summary, aerobic training provided better protection against knee joint OA than resistance training in this rat model of HFS-diet-induced obesity. Exposing rats to exercise, either aerobic or resistance training, had a protective effect against the severe bone lesions observed in the nonexercised rats.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"453-460"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185796","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}
{"title":"Upregulated Mitochondrial Dynamics Is Responsible for the Procatabolic Changes of Chondrocyte Induced by α2-Adrenergic Signal Activation.","authors":"Jiaying He, Wenpin Qin, Yusong Zhang, Jianfei Yan, Xiaoxiao Han, Jialu Gao, Qihong Li, Kai Jiao","doi":"10.1177/19476035231189841","DOIUrl":"10.1177/19476035231189841","url":null,"abstract":"<p><strong>Objective: </strong>Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study.</p><p><strong>Design: </strong>Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated.</p><p><strong>Results: </strong>We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE.</p><p><strong>Conclusions: </strong>The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that \"α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes\" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"440-452"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10468288","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}
CARTILAGEPub Date : 2024-12-01Epub Date: 2023-08-24DOI: 10.1177/19476035231193089
Conner W Hutcherson, Michelle Mao, Bhaskar Thakur, Yasin Y Dhaher
{"title":"Low-Grade Inflammatory Mediators and Metalloproteinases Yield Synchronous and Delayed Responses to Mechanical Joint Loading.","authors":"Conner W Hutcherson, Michelle Mao, Bhaskar Thakur, Yasin Y Dhaher","doi":"10.1177/19476035231193089","DOIUrl":"10.1177/19476035231193089","url":null,"abstract":"<p><strong>Objective: </strong>Mechanical loading is an essential factor for the maintenance of joint inflammatory homeostasis and the sensitive catabolic-anabolic signaling cascade involved in maintaining cartilage tissue health. However, abnormal mechanical loading of the joint structural tissues can propagate joint metabolic dysfunction in the form of low-grade inflammation. To date, few studies have attempted to delineate the early cascade responsible for the initiation and perpetuation of stress-mediated inflammation and cartilage breakdown in human joints.</p><p><strong>Design: </strong>Fifteen healthy human male participants performed a walking paradigm on a cross-tilting treadmill platform. Blood samples were collected before exercise, after 30 minutes of flat walking, after 30 minutes of tilted walking, and after an hour of rest. Serum concentrations of the following biomarkers were measured: interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, transforming growth factor beta (TGF)-β, tissue inhibitor of matrix metalloproteinase 1 (TIMP)-1, and cartilage oligomeric protein (COMP).</p><p><strong>Results: </strong>Luminex Multiplex analysis of serum showed increased concentrations of COMP, IL-1β, TNF-α, IL-10, and TGF-β from samples collected after flat and cross-tilted treadmill walking compared to baseline. Serum concentrations of MMP-1 and MMP-13 also increased, but primarily in samples collected after tilted walking. Pearson's correlation analysis showed positive correlations between the expression of COMP, TNF-α, IL-10, and MMP-13 at each study timepoint.</p><p><strong>Conclusion: </strong>Stress-mediated increases in serum COMP during exercise are associated with acute changes in pro and anti-inflammatory molecular activity and subsequent changes in molecules linked to joint tissue remodeling and repair.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"417-427"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10415530","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}
CARTILAGEPub Date : 2024-12-01Epub Date: 2024-02-25DOI: 10.1177/19476035241233441
Avanish Yendluri, Ara Alexanian, Rohit R Chari, John J Corvi, Nikan K Namiri, Junho Song, Michael J Alaia, Xinning Li, Robert L Parisien
{"title":"The Statistical Fragility of Marrow Stimulation for Cartilage Defects of the Knee: A Systematic Review of Randomized Controlled Trials.","authors":"Avanish Yendluri, Ara Alexanian, Rohit R Chari, John J Corvi, Nikan K Namiri, Junho Song, Michael J Alaia, Xinning Li, Robert L Parisien","doi":"10.1177/19476035241233441","DOIUrl":"10.1177/19476035241233441","url":null,"abstract":"<p><strong>Objective: </strong>Marrow stimulation is used to address knee cartilage defects. In this study, we used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate statistical fragility of outcomes reported in randomized controlled trials (RCTs) evaluating marrow stimulation.</p><p><strong>Design: </strong>PubMed, Embase, and MEDLINE were queried for recent RCTs (January 1, 2010-September 5, 2023) assessing marrow stimulation for cartilage defects of the knee. The FI and rFI were calculated as the number of outcome event reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The FQ was determined by dividing the FI by the study sample size.</p><p><strong>Results: </strong>Across 155 total outcomes from 21 RCTs, the median FI was 3 (interquartile range [IQR], 2-5), with an associated median FQ of 0.067 (IQR, 0.033-0.010). Thirty-two outcomes were statistically significant, with a median FI of 2 (IQR, 1-3.25) and FQ of 0.050 (IQR, 0.025-0.069). Ten of the 32 (31.3%) outcomes reported as statistically significant had an FI of 1. In total, 123 outcomes were nonsignificant, with a median rFI of 3 (IQR, 2-5). Studies assessing stem cell augments were the most fragile, with a median FI of 2. In 55.5% of outcomes, the number of patients lost to follow-up was greater than or equal to the FI.</p><p><strong>Conclusion: </strong>Statistical findings in RCTs evaluating marrow stimulation for cartilage defects of the knee are statistically fragile. We recommend combined reporting of <i>P</i>-values with FI and FQ metrics to aid in the interpretation of clinical findings in comparative trials assessing cartilage restoration.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"389-398"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971086","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}