Arthritis & Rheumatology最新文献

{"title":"The Effect of Benralizumab and Mepolizumab on Use of Oral Glucocorticoids in Patients with Eosinophilic Granulomatosis with Polyangiitis.","authors":"Parameswaran K Nair,Bernhard Hellmich,Arnaud Bourdin,David R W Jayne,Florence Roufosse,Nader Khalidi,Lena Börjesson Sjö,Ying Fan,Christopher McCrae,Sofia Necander,Eva Rodríguez-Suárez,Anat Shavit,Claire Walton,Peter A Merkel,Michael E Wechsler","doi":"10.1002/art.43398","DOIUrl":"https://doi.org/10.1002/art.43398","url":null,"abstract":"OBJECTIVEThe Phase 3 MANDARA study demonstrated non-inferiority of benralizumab versus mepolizumab for remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). More benralizumab-treated patients achieved complete withdrawal of oral glucocorticoids (OGCs). These post-hoc analyses further elucidate the efficacy of benralizumab and mepolizumab in facilitating reductions in OGCs.METHODSAdults with EGPA requiring ≥7.5 mg/day OGC ±immunosuppressive therapy were randomized to benralizumab 30mg (n=70) or mepolizumab 300mg (n=70) subcutaneously every 4 weeks for 52 weeks. Investigators tapered OGCs for patients with stable EGPA based on clinical judgment. Reductions in OGC use (to ≤4mg/day, by ≥50%, or complete withdrawal) were considered sustained if achieved by Week 40 and maintained through Week 52.RESULTSThe 12-month cumulative dose of OGC was ~1,800 mg in both groups. At Weeks 49-52, the median (minimum-maximum) OGC dose was 1.16 (0.0-16.6) and 3.00 (0.0-25.7) mg/day for benralizumab and mepolizumab, respectively. Time to first or sustained OGC reduction to ≤4mg/day or by ≥50%, and accrued OGC-free duration, were similar between groups. More benralizumab- than mepolizumab-treated patients completely withdrew OGCs (33/70 vs 20/70; HR for time to first complete withdrawal 1.84 [95% CI, 1.06, 3.27], unstratified log-rank test p=0.0291) and sustained complete withdrawal (17/70 vs 7/70; HR for time to reduction 2.97 [95%CI: 1.26,7.77], unstratified log-rank test p=0.0268). In both groups, complete OGC withdrawal was similar across patient subgroups, including by ANCA status and immunosuppressive use.CONCLUSIONTargeting the interleukin-5 receptor with benralizumab, or circulating interleukin-5 with mepolizumab, are effective OGC-sparing strategies in patients with EGPA.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"39 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of time to start of biologic therapy on treatment response in childhood arthritis: Results from the UCAN CAN-DU study.","authors":"Jelleke B de Jonge,Sytze de Roock,Dieneke Schonenberg-Meinema,J Merlijn van den Berg,Deborah A Marshall,Sebastiaan J Vastert,Rae S M Yeung,Joost F Swart,Susanne M Benseler, ","doi":"10.1002/art.43401","DOIUrl":"https://doi.org/10.1002/art.43401","url":null,"abstract":"","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"162 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy and safety of anakinra and canakinumab in patients with VEXAS syndrome - an international multicenter study.","authors":"Tali Eviatar,Dafne Capelusnik,Corrado Campochiaro,Valentin Lacombe,Vincent Jachiet,Michael Zisapel,Iftach Sagy,Oshrat E Tayer-Shifman,David Ozeri,Shaye Kivity,Alessandro Tomelleri,Benjamin Terrier,Hagit Peleg,Thibault Comont,Karim Sacre,Pascal Woaye-Hune,Laurent Arnaud,Estibaliz Lazaro,Vincent Grobost,Francois Lifermann,Maxime Samson,Samuel Ardois,Alice Garnier,Alexandre Maria,Alain Cantagrel,Aurore Meyer,Jean-David Bouaziz,Mael Heiblig,Lorenzo Dagna,Elisa Diral,Olivier Kosmider,Ori Elkayam,Jérôme Hadjadj,Sophie Georgin-Lavialle,Olivier Fain,Arsene Mekinian","doi":"10.1002/art.43384","DOIUrl":"https://doi.org/10.1002/art.43384","url":null,"abstract":"OBJECTIVESThe aim of this study was to compare differences in clinical response, drug survival, and adverse event rates between anakinra and canakinumab in VEXAS syndrome.METHODSThis multicenter international study includes VEXAS patients from France, Israel, and Italy treated with IL1 inhibition (IL1i). Global response (GR) was defined as the absence of inflammatory symptoms, 50% or greater decrease in steroid dose and C-reactive protein. Multiple regression analysis was performed to identify associated variables. Drug survival was analyzed using Kaplan-Meier plots and log-rank test, with Cox-regression models for associated factors.RESULTSWe included 47 male VEXAS patients; 44 received anakinra, and 9 received canakinumab, with 6 patients using both at different time points. GR at 1 month was 34% for anakinra and 100% for canakinumab (p<0.001), 22% and 78% at 3 months, respectively (p=0.001). Treatment with canakinumab was associated with higher odds ratio (OR) of achieving GR at 3 months (OR 28.8, 95%CI 3·0-273·9, p=0.004) in a multivariable analysis. Median drug survival was 54 (30-56) months for canakinumab at 300 mg/month, compared to 7 (4-8) months for canakinumab 150 mg/month and 1 (1-2.5) months for anakinra (p=0.01). Injection site reactions were only recorded for the anakinra group (47 vs 0%; p=0.006), whereas infections were more frequent in the anakinra group (31% and 11%; p=0·3).CONCLUSIONSCanakinumab demonstrated superior clinical response and drug survival with fewer adverse events compared to anakinra. Monthly Canakinumab 300 mg may be considered as an effective steroid-sparing therapeutic option for VEXAS patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"196 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomere Length of Peripheral Blood Leukocytes Predicts Disease Severity and Worse Survival in Systemic Sclerosis.","authors":"Monica M Yang,Shuo Liu,Michael Wax,Seoyeon Lee,Sarah French,Paul J Wolters,Francesco Boin","doi":"10.1002/art.43400","DOIUrl":"https://doi.org/10.1002/art.43400","url":null,"abstract":"OBJECTIVEPeripheral blood leukocyte telomere length (PBL-TL) shortening is associated with systemic sclerosis related interstitial lung disease (SSc-ILD). However, its association with other organ involvement, disease severity, and survival remains unclear. This study aimed to define the relationship of TL with SSc-specific disease manifestations and outcomes.METHODPBL-TL was measured by quantitative PCR in 244 patients with SSc and 314 healthy controls. Multivariate modeling was utilized to assess the association of PBL-TL with disease severity and event-free survival. Longitudinal changes in PBL-TL were measured in a subset of patients. Telomere length was quantified in SSc skin and lung tissues by telomere fluorescence in situ hybridization.RESULTSPBL-TL was significantly shorter in patients with SSc than healthy controls. Shortened PBL-TL was associated with presence and severity of ILD and pulmonary hypertension (PH) with the shortest PBL-TL found in subjects with concurrent ILD and PH (p=0.04). PBL-TL was not associated with skin disease or peripheral vascular disease. Shorter PBL-TL was associated with hospitalizations (p<0.01) and worse event-free survival (p=0.03). Patients with early SSc had a faster rate of PBL-TL shortening compared to patients with longer disease duration (p = 0.04). TL was shorter in SSc-ILD lung epithelial cells (p=0.01) while no difference was found in epithelial cells of SSc skin (p=0.82).CONCLUSIONShort PBL-TL is associated with pulmonary disease severity and predicts worse SSc clinical outcomes. This study provides rationale to further investigate the role of telomere dysfunction in SSc pathogenesis and validate TL as a prognostic biomarker in SSc.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"63 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transition from psoriasis to psoriatic arthritis is characterized by distinct alterations in peripheral blood Tc17, Th17 and CD4+ TEM cells.","authors":"Hanna Graßhoff,Sara Comdühr,Henry Nording,Jacob von Esebeck,Philine Letz,Miriam Prohaczka,Handan Gedik,Henner Zirpel,Elisabeth Spallek,Linh Ha-Wissel,El-Baraa Adjailia,Sabrina Arnold,Konstantinos Fourlakis,Sebastian Klapa,Ingo Eitel,Oliver J Müller,Jens Y Humrich,Gabriela Riemekasten,Diamant Thaçi,Peter Lamprecht","doi":"10.1002/art.43396","DOIUrl":"https://doi.org/10.1002/art.43396","url":null,"abstract":"OBJECTIVECellular mechanisms driving transition from psoriasis to psoriatic arthritis have remained largely elusive. Thus, we investigated changes within the peripheral blood T cell compartment associated with the transition phase.METHODSIn an observational study, 116 patients were examined and categorized into subgroups including psoriasis with at least one risk factor for transition to psoriatic arthritis, subclinical psoriatic arthritis according to EULAR taskforce recommendations from 2023, and definitive psoriatic arthritis meeting the CASPAR criteria. Demographic and clinical characteristics of patient subgroups were analyzed. Deep T cell phenotyping using multicolor flow cytometry and machine learning techniques were applied.RESULTSOverlapping T cell endotypes were found among patients with subclinical psoriatic arthritis exhibiting the most notable divergence from the others. Frequencies of effector memory CD4+ T (TEM) cells, T helper 17 (Th17) and T cytotoxic 17 (Tc17) cells differed between psoriasis with at least one risk factor for transition, subclinical psoriatic arthritis and psoriatic arthritis. Transition-associated changes of Tc17 cell frequencies were confirmed by machine learning-assisted unsupervised clustering analysis. Moreover, patients with enthesitis could be distinguished from those without, with Tc17 cells being the main distinctive feature.CONCLUSIONTransition from psoriasis to psoriatic arthritis was associated with distinct alterations of the peripheral blood T cell compartment with Tc17 cells exhibiting the greatest discriminatory power. These findings provide insight into pathomechanisms driving disease progression during transition from psoriasis to psoriatic arthritis and identify Tc17 cells as foremost novel potential therapeutic target for the prevention of transition.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"77 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of an Idiopathic Pulmonary Fibrosis Derived Multibiomarker Panel for Rheumatoid Arthritis-Associated Interstitial Lung Disease.","authors":"Brent A Luedders,Daniel Kass,Joshua F Baker,Michael J Duryee,Yangyuna Yang,Punyasha Roul,Halie Frideres,Katherine D Wysham,Paul A Monach,Andreas Reimold,Gail S Kerr,Gary Kunkel,Grant W Cannon,Scott M Matson,Jill A Poole,Geoffrey M Thiele,Ted R Mikuls,Bryant R England,Dana P Ascherman","doi":"10.1002/art.43383","DOIUrl":"https://doi.org/10.1002/art.43383","url":null,"abstract":"OBJECTIVETo assess whether a panel of peripheral blood biomarkers associated with idiopathic pulmonary fibrosis (IPF) is also associated with interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) utilizing three independent cohorts.METHODSWe first assessed the association of a panel of IPF-associated biomarkers with prevalent ILD among two separate RA cohorts (n=93 and n=71). Concentrations of eight IPF-related biomarkers (eotaxin, Flt-3L, IL-8, MDC, MCP-1, and MMP-2/7/9) were measured, standardized, and summed to generate a multibiomarker score. We subsequently validated the association of this score (minus MMP-2) with prevalent and incident ILD in an independent multicenter, prospective cohort of US Veterans with RA (n=2,507). Multivariable regression models were adjusted for relevant covariates in the validation cohort.RESULTSIn both development cohorts, participants with RA-ILD had significantly higher IPF multibiomarker scores than those with RA alone. In the independent validation cohort, participants with the highest quartile multibiomarker scores had a significantly higher likelihood of prevalent ILD (adjusted odds ratio 2.14 [95% CI 1.18-3.87]) and incident ILD (adjusted hazard ratio 2.45 [95% CI 1.55-3.88]) than those in the lowest quartile. The cumulative hazard of incident ILD approached 20% by 15 years for those in the highest quartile compared to <10% for all other quartiles.CONCLUSIONA multibiomarker panel derived from IPF-associated biomarkers was associated with RA-ILD in separate development and validation cohorts. This overlap supports the concept of shared etiopathogenesis of IPF and RA-ILD and illustrates the potential for peripheral blood biomarker panels to stratify ILD risk among RA patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"19 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomized, placebo-controlled trial of hydroxychloroquine in incomplete lupus.","authors":"Nancy J Olsen,Duanping Liao,Judith A James,Joel M Guthridge,Cristina Arriens,Diane Kamen,Mariko Ishimori,Daniel J Wallace,Christopher Striebich,Sonali Narain,Benjamin F Chong,Fan He,Eric W Schaefer,Vernon M Chinchilli,David R Karp","doi":"10.1002/art.43391","DOIUrl":"https://doi.org/10.1002/art.43391","url":null,"abstract":"OBJECTIVESPatients with features of systemic lupus erythematosus (SLE) who do not fulfill classification criteria can be designated as incomplete lupus (ILE). This condition includes individuals with a high risk of progression to SLE. Treatment of ILE may reduce symptoms, severity and incidence of SLE.METHODSHydroxychloroquine (HCQ) was chosen as an ILE intervention for a randomized, double-blind trial to determine whether rate of accumulation of SLE features defined by the 2012 SLICC criteria could be reduced. ILE was defined as ANA positivity with 1-2 additional criteria. Patients 15-49 years old were eligible. Randomization was 1:1 HCQ to placebo. Evaluations were at 3-month intervals over 24 months. Meeting SLICC classification sooner required exit.RESULTSParticipants (n=187) were randomized at 7 sites. After excluding 7 patients who met SLE classification at baseline when screening laboratory data were completed, 180 patients were analyzed: 92 on HCQ and 88 on placebo. The mean age was 33 years, 91.1% were female and 74.4% were white. SLE classification developed in 24 (13.3%); another 24 developed additional criteria but did not meet classification. The rates of acquisition of SLICC criteria and progression to SLE were similar in the two groups (P=0.72 and P=0.98, respectively). Development of SLE was associated with new malar rash, oral ulcers, joint tenderness or pleurisy (P<0.04).CONCLUSIONWhile SMILE did not show effects of HCQ on ILE progression, the results offer insights into SLE risk in the ILE population. With development of biomarkers, designing targeted prevention strategies should be feasible.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"83 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stromal Cell Therapy Alleviates Lupus Nephritis Through Inhibiting Caspase-4/5/11-mediated Noncanonical Pyroptosis in Macrophages.","authors":"Sha Liu,Zhikang Wang,Yue Zhang,Panpan Zhou,Huimin Zhu,Yang Hang,Xue Xu,Xiaojun Tang,Genhong Yao,Dandan Wang,Linyu Geng,Weiwei Chen,Lingyun Sun","doi":"10.1002/art.43380","DOIUrl":"https://doi.org/10.1002/art.43380","url":null,"abstract":"BACKGROUNDCaspase-4/5/11 mediated noncanonical pyroptosis emerges as a contributing factor in immune responses under pathological conditions. However, its precise role in the development of lupus nephritis (LN) remains largely unknown. Although mesenchymal stromal cells (MSCs) have demonstrated promising therapeutic effects on LN, whether MSCs influence pyroptosis in macrophages remains unknown. This study aimed to elucidate the role of caspase-4/5/11-mediated noncanonical pyroptosis in macrophages during the pathogenesis of LN and explore the impact of MSCs on macrophages.METHODSThe expression level of noncanonical pyroptosis in macrophages was assessed in patients and mice with LN. Blood samples from 19 refractory SLE patients receiving MSCs transplantation (MSCT) were collected. Caspase-11 inhibitor wedelolactone and MSCs were administered to MRL/lpr mice to examine the therapeutic efficacy. MSCs were co-cultured with macrophages from MRL/lpr mice to explore effects and related mechanisms.RESULTSNoncanonical pyroptosis signaling was activated in macrophages and kidney tissues from humans and mice with LN. The expression level of caspase-4 was increased and positively correlated with the active index and chronic index in the kidneys of LN patients. The end products of pyroptosis directly induced cell death and reduced functional markers expression in murine podocytes. The caspase-11 inhibitor effectively alleviated renal damage in lupus mice. MSCT significantly deactivated pyroptosis signaling both in patients and lupus-prone mice. Mechanically, galectin-3 and interleukin-10 (IL-10) are essential for MSCs to inhibit noncanonical pyroptosis of LN macrophages.CONCLUSIONSOur findings showed that MSCT ameliorates LN by inhibiting the caspase-4/5/11-mediated pyroptosis in macrophages, possibly via secreting galectin-3 and IL-10.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"35 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-23 receptor deficiency in podocytes averts the development of lupus nephritis.","authors":"Rong Fu,Afroditi Boulougoura,Shuilian Yu,Hao Li,Wenliang Pan,Yushiro Endo,Rhea Bhargava,Abhiyan Satyam,Vivek Kasinath,Jarrat Jordan,Nandan Padmanabha,Maria G Tsokos,Reza Abdi,George C Tsokos","doi":"10.1002/art.43395","DOIUrl":"https://doi.org/10.1002/art.43395","url":null,"abstract":"OBJECTIVEUpregulation of Interleukin 23 (IL-23) in the serum and kidneys of patients with lupus nephritis (LN) has been demonstrated, but its effect on podocytes remains unknown. We hypothesized that IL-23 contributes to podocyte injury and that targeted deletion of IL-23R in podocytes of lupus-prone mice can prevent the development of glomerulonephritis.METHODSKidney biopsies were immunostained for IL-23R. In vitro experiments were conducted using a human podocyte cell line and primary murine podocytes. Human podocytes stimulated with IL-23 underwent bulk-RNA sequencing. The expression of IL-23R, structure and motility of podocytes were assessed. Podocytes isolated from B6 wild type mice injected with a minicircle (MC) encoding IL-23 were studied. To assess the role of IL-23R in the development of nephritis, we generated podocyte-specific Il23r deficient MRL/lpr lupus-prone mice.RESULTSIL-23R was highly expressed in the glomeruli of patients with LN. IL-23R expression was also upregulated in human podocytes and primary podocytes isolated from B6 mice after IL-23 stimulation. Human podocytes stimulated with IL-23 showed decreased expression of synaptopodin and remodeling of the actin cytoskeleton. IL-23 MC-administered mice exhibited a significant increase in the expression of IL-23R and phosphorylated STAT3 (pSTAT3) in podocytes. Finally, MRL/lpr.Podo-Cre+ Il23rfl/fl mice showed decreased clinical and histologic features of LN.CONCLUSIONIL-23R expression is increased in podocytes from mice and humans with systemic lupus erythematosus. IL-23 signaling disrupts the cytoskeleton in podocytes and increases their mobility leading to the development of glomerulonephritis. Podocyte-specific deletion of Il23r in lupus-prone mice abrogates the development of LN.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"76 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZBTB20 Regulating Postnatal Articular Cartilage Development and Homeostasis: Implications for Early-Onset Osteoarthritis.","authors":"Xianhua Ma,Fei Jiang,Zhenbang Qin,Yuqing Zhang,Chunchun Wei,Shuang Han,Yuxia Chen,Hai Zhang,Jiang Tao,Zhifang Xie,Weiping J Zhang","doi":"10.1002/art.43393","DOIUrl":"https://doi.org/10.1002/art.43393","url":null,"abstract":"OBJECTIVEMutations in ZBTB20, a transcription factor, are linked to epiphyseal dysplasia and articular degeneration in humans. This study investigates the role of ZBTB20 in regulating articular cartilage growth and integrity during postnatal development and its implications for early-onset osteoarthritis (OA) in mice.METHODSWe assessed the spatiotemporal expression of ZBTB20 in articular cartilage using immunostaining and generated an inducible cartilage-specific Zbtb20 knockout mouse model. The impacts of Zbtb20 deletion on cartilage thickness, zonal organization, cellular proliferation, and apoptosis were analyzed. We employed histology, Micro-CT, in situ hybridization, RNA-sequencing, and CUT&Tag to evaluate structural and molecular changes in knees from six to eight male mice per group. ZBTB20 expression in human OA cartilage was analyzed using publicly available datasets.RESULTSZBTB20 was expressed in postnatal developing and adult articular chondrocytes. Postnatal Zbtb20 deletion resulted in progressive thickening of articular cartilage in knees, with a 1.9-fold increase at 2 months of age, particularly in the deep and calcified zones. This was accompanied by chondrocyte overproliferation and differentiation defects, leading to early-onset cartilage degeneration by 6 months. RNA-sequencing and CUT&Tag analyses revealed that ZBTB20 directly regulates a broad set of genes essential for cartilage growth, chondrocyte differentiation, and extracellular matrix organization. Moreover, ZBTB20 expression was significantly reduced in aging-related OA cartilage in both mice and humans, and inducible deletion of Zbtb20 in adult cartilage resulted in severe spontaneous OA-like changes in mice.CONCLUSIONZBTB20 is essential for postnatal articular cartilage development and homeostasis, with a protective role in aging-related OA progression.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"52 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}