Introduction:To investigate the metabolism and distribution of iPSC-MSCs in the joint cavity of rats with knee osteoarthritis (KOA). Methods:The iPSC-MSCs labeled with the Antares2 luciferase gene were injected into the knee joints of rats, and then the metabolism and distribution of the cells in vivo were revealed by imaging and molecular biomarker methods. Result:Histopathological results demonstrated that iPSC-MSCs significantly reversed joint tissue damage of arthritic rats. The fluorescence signal of iPSC-MSCs labeled with Antares2 luciferase gene was stable and persistent with high detection sensitivity. The fluorescent signal duration of Antares2-iMSCs in the joint cavity of KOA rats was approximately 2 weeks, which was significantly longer than 1 week in the sham-operated group. The proportion of iPSC-MSCs in the synovial fluid gradually decreased over time, and for the first time, the cells were observed to attach to the synovium first, followed by the meniscus and cartilage. Discussion:This study was the first to explore the metabolism and distribution of iPSC-MSCs after intra-articular injection by labeling the Antares2 luciferase gene, which provides assurance and theoretical basis for the safety of clinical application of iPSC-MSCs in treating osteoarthritis.

ABSTRACTBackgroundAirway inflammation is considered one of the pathogenic factors in rheumatoid arthritis (RA), but the role of chronic obstructive pulmonary disease (COPD) in the development of RA remains unclear. We used cross‐sectional studies and Mendelian randomization (MR) analysis to explore the link between COPD and RA.MethodsIn National Health and Nutrition Examination Survey (NHANES) 2013–2018, the association between COPD and RA was investigated using weighted logistic regression models. We also used subgroup analysis and interaction tests to explore the relationship between COPD and RA in populations with different clinical characteristics. The inverse‐variance weighted (IVW) method was the primary method of MR analysis for investigating the causal effect of exposure on outcome.ResultsAfter adjusting for smoking history and other variables, weighted logistic regression analysis of 14 768 participants indicated that COPD is associated with an increased odds of developing RA (OR = 1.899, p < 0.001). Interaction tests showed that there is an interaction with this relationship concerning gender, age, body mass index (BMI), and hypercholesterolemia (p < 0.05). MR analysis showed a causal relationship between COPD and increased odds of RA (OR = 1.072, p = 0.008). Multivariable MR analysis, adjusted for smoking, also yielded the same result (OR = 1.071, p = 0.024).ConclusionOur study suggests that COPD may have a potential causal role in the development of RA. Further research is needed to validate our findings.

Importance:A recent study reported that methotrexate may reduce joint pain in patients with inflammatory hand osteoarthritis (OA). However, it remains unknown whether methotrexate has similar effects on inflammatory knee OA. Objective:To examine whether methotrexate has symptom-relieving and disease-modifying effects for participants with knee OA and effusion-synovitis. Design, Setting, and Participants:This multicenter, placebo-controlled randomized clinical trial was conducted at 11 sites in China between July 18, 2019, and January 15, 2023. Community-dwelling patients with inflammatory knee OA with effusion-synovitis on magnetic resonance imaging were included. Interventions:Participants were randomly assigned (1:1) to receive methotrexate, up to 15 mg weekly, or placebo using block randomization, stratified by study site. Main Outcomes and Measures:The primary outcomes were knee visual analog scale (VAS) pain change and effusion-synovitis maximal area change, over 52 weeks in the intention-to-treat population. Results:Of 278 participants screened, 215 participants (mean [SD] age, 60.4 [7.4] years; 191 [89%] female) were randomized (108 to the methotrexate group; 107 to the placebo group), and 175 (81%) completed the trial. Changes in VAS pain and effusion-synovitis maximal area were not significantly different between the methotrexate and placebo group over 52 weeks (between-group difference, 0.3 mm [95% CI, -6.7 to 7.3 mm] for VAS pain; 0.1 cm2 [95% CI, -0.8 to 1.0 cm2] for effusion-synovitis maximal area). No significant between-group differences were found for any of the prespecified secondary outcomes. At least 1 adverse event occurred in approximately 32 participants (29.6%) in the methotrexate group and 26 participants (24.3%) in the placebo group. Conclusions and Relevance:The results of this randomized clinical trial show that, compared to placebo, low-dose methotrexate did not reduce pain or effusion-synovitis over 52 weeks in patients with knee OA and effusion-synovitis. Trial Registration:ClinicalTrials.gov Identifier: NCT03815448.

Nuclear transcription factor-κB (NF-κB) activation is a pivotal event in the pathogenesis of osteoarthritis (OA). OA patients frequently exhibit vitamin D (VD) deficiency, which is commonly associated with NF-κB activation. Our study aimed to investigate whether VD could protect against OA by modulating NF-κB pathway and to explore the underlying mechanisms. Proteins levels were assessed by western blot analysis, gene expression was quantified by quantitative real-time polymerase chain reaction (qRT‒PCR) in vivo and in vitro. The expression of phosphorylated-p65 (p-p65) in knee OA rats was detected by immunohistochemistry, and an NF-κB nuclear translocation assay was validated in chondrocytes. Immunoprecipitation was employed to detect the interaction between NF-κB and vitamin D receptor (VDR) in vivo and in vitro. Small interfering RNA (Si-NF-κB and Si-VDR) transfection was used to investigate the role of NF-κB and VDR signaling pathway in knee OA rats under VD influence. Cartilage changes were visualized of knee OA rats using hematoxylin and eosin as well as safranin-O/fast green of staining. Our findings indicated that VD alleviates OA by inhibiting NF-κB pathway, which in turn reduces chondrocyte apoptosis and extracellular matrix (ECM) degradation. Further analysis revealed that VD primarily stabilizes NF-κB through the interaction of VDR and NF-κB, modulating the AMPK/mTOR signaling pathway to enhance autophagy and delay the progression of OA. This study highlights the protective role of VD in OA by stabilization of NF-κB, mainly through the interaction between VDR and NF-κB. This interaction regulates the AMPK/mTOR signaling pathway, promoting autophagy and suggesting a potential therapeutic strategy for OA management.

BACKGROUND:Multicentric reticulohistiocytosis (MRH)/systemic lupus erythematosus (SLE) overlap syndrome is an uncommon disease in the clinic and is diagnosed through characteristic clinical manifestations, histopathology, and immunopathology. Here, we report the case of a 30-year-old woman with SLE who developed MRH.CASE SUMMARY:A 30-year-old woman with a history of polyarthritis for the past 12 years had multiple skin nodules on her body for 10 years, including the sacrococcygeal area, dorsum of the hands, interphalangeal joint of the feet and sternoclavicular joint. The histopathology of a biopsy of the distal interphalangeal joint of the hands revealed granulomatous inflammation, fibrous hyperplasia with ground-glass degeneration, inflammatory cell exudation and focal necrosis. The immunohistochemical stains showed positive staining for CD68 and negative staining for S100 and acid-fast staining. The patient was diagnosed with SLE with MRH. Her symptoms were improved after a combined treatment of prednisone, hydroxychloroquine and cyclophosphamide.CONCLUSION:MRH/SLE overlap syndrome is difficult to diagnose and treat. Cyclophosphamide may be an alternative choice for the treatment of MRH.

Abstract Introduction Systemic lupus erythematosus (SLE) complicated by multiple myeloma (MM) is a relatively rare clinical presentation, and is easily ignored due to their similar or even identical manifestation, which may lead to misdiagnosis and mistreatment. Case report We report two cases of SLE with MM. Case 1 was a 59‐year‐old male who was diagnosed with SLE 11 years ago. Abnormal kidney function was detected 4 months ago and a bone marrow aspirate revealed MM. He then received three cycles of bortezomib, dexamethasone, and chemotherapy with liposomal doxorubicin, and one cycle of lenalidomide plus dexamethasone. He died of infectious shock. Case 2 was a 58‐year‐old female who was diagnosed with SLE 27 years ago. After the onset of abnormal renal function 4 years ago, the patient was still treated according to SLE disease activity. When renal function rapidly deteriorated, serum and urine immunofixation electrophoresis was positive for IgG γ with free light chains and she was diagnosed with SLE complicated by MM. She did not agree to the treatment for MM as advised and was discharged from the hospital against medical advice. Case 2 died of cardiac failure. Thirteen cases of SLE with MM reported from 2000 to 2022 in PUBMED and Mendeley and our above two cases were reviewed. Among the 15 patients, 13 were females and 2 were males. The median age at the time of SLE with MM diagnosis was 50 years, and the median time to a delayed diagnosis was 7 years. The serum monoclonal immunoglobulin level was elevated and extramedullary manifestations of renal dysfunction were common. Conclusions An elevated monoclonal immunoglobulin level or newly unexplained renal dysfunction occurring in a patient with SLE should prompt monitoring and further screening of MM, rather than treatment as a secondary manifestation of SLE.

目的 探讨膝骨关节炎(OA)患者血清白细胞介素(IL)-18水平与关节软骨体积、软骨缺损、骨髓病变(BML)和软骨降解生物标志物之间的横断面相关性,为临床诊治提供新思路和新方法.方法 该研究纳入151例膝OA患者,采用问卷调查采集患者一般信息,通过核磁共振成像(MRI)完成膝关节摄片,用OsiriX软件以3D-FLASH序列测量软骨体积,用T2加权序列半定量测定软骨缺损和B ML.酶联免疫吸附法(ELISA)检测血清IL-18和基质金属蛋白酶(MMP)-3、MMP-13水平.使用SPSS软件进行统计分析.结果 在多变量分析中,血清IL-18水平与总软骨体积呈显著负相关(β=-0.24,95％CI:-0.13～0.03),与不同关节部位的软骨体积(胫骨和髌骨,P<0.05)的相关性一致.血清IL-18水平与股骨内侧的软骨缺损及BML呈正相关(P<0.01).血清IL-18水平与MMP-3(β=0.31,95％CI:0.001～0.010)和MMP-13(β=0.86,95％CI:0.08～0.10,P<0.01)水平呈正相关.结论 血清IL-18水平与膝OA软骨体积呈负相关,与软骨缺损、BML、MMP-3和MMP-13呈正相关,提示IL-18可能在膝OA患者软骨病变中起显著作用,靶向血清IL-18的治疗可能减少膝OA患者关节软骨损伤,延缓疾病进展.

OBJECTIVES:The deletion of chondrocyte autophagy seems to play a key role in the pathogenesis of osteoarthritis (OA). Patients with OA often have vitamin D (VD) deficiency, and VD supplementation can improve pain and alleviate the progression of joint structures in patients. In this study, we aimed to investigate whether VD could enhance autophagy by activating the adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signalling pathway and protect against OA.METHODS:In this study, the levels of target proteins and genes were examined by western blot and qRT-PCR. Apoptotic cells were detected using TUNEL staining. Characteristics of autophagy were observed by LysoTracker red staining, mRFP-GFP-LC3 adenovirus transfection, and transmission electron microscopy. siRNA-mediated AMPK and mTOR knockdown were used to investigate the role of the AMPK/ mTOR signalling pathway in VD-induced autophagy. Haematoxylin and eosin and safranin-O/fast green staining were used detect cartilage alterations.RESULTS:We suggested that VD significantly reduced chondrocyte death and alleviated extracellular matrix degradation. Further studies showed that VD promoted the expression of the autophagy-related protein LC3II through the AMPK/mTOR signalling pathway in chondrocytes, activated lysosome activity, promoted the formation of autophagy-associated lysosomes, which played a crucial role in the degradation of intracellular organelles and maintained homeostasis. The anti-apoptotic effect of VD on chondrocytes was associated with the activation of autophagy. The group of AMPK-normal and mTOR-knockdown in the presence of VD inhibited chondrocyte apoptosis by promoting autophagy.CONCLUSIONS:This study highlights that VD can activate chondrocyte autophagy through the AMPK/mTOR signalling pathway.

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease. Despite the wide use of conventional synthetic, targeted and biologic disease modifying anti-rheumatic drugs (DMARDs) to control its radiological progress, nearly all DMARDs are immunologically non-selective and do not address the underlying immunological mechanisms of RA. Patients with RA often need to take various DMARDs long-term or even lifelong and thus, face increased risks of infection, tumor and other adverse reactions. It is logical to modulate the immune disorders and restore immune balance in patients with RA by restoring immune tolerance. Indeed, approaches based on stem cell transplantation, tolerogenic dendritic cells (tolDCs), and antigen-based tolerogenic vaccination are under active investigation, and some have already transformed from wet bench research to clinical investigation during the last decade. Among them, clinical trials on stem cell therapy, especially mesenchymal stem cells (MSCs) transplantation are most investigated and followed by tolDCs in RA patients. On the other hand, despite active laboratory investigations on the use of RA-specific peptide-/protein-based tolerogenic vaccines for T cell, clinical studies on RA patients are much limited. Overall, the preliminary results of these clinical studies are promising and encouraging, demonstrating their safety and effectiveness in the rebalancing of T cell subsets; particular, the recovery of RA-specific Treg with increasing anti-inflammatory cytokines and reduced proinflammatory cytokines. Future studies should focus on the optimization of transplanted stem cells, the preparation of tolDCs, and tolerogenic vaccines with RA-specific protein or peptide, including their dosage, course, and route of administration with well-coordinated multi-center randomized clinical control researches. With the progress of experimental and clinical studies, generating and restoring RA-specific immune tolerance may bring revolutionary changes to the clinical management of RA in the near future.

The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0-2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m(2)/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2-3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m(2)/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).

Background Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid- to late-stage KOA. Methods/design This protocol describes a multicentre randomised placebo-controlled clinical trial aiming to recruit 200 participants with mid- to late-stage symptomatic KOA and with effusion-synovitis grade of ≥ 2. Participants will be randomly allocated to the MTX group (start from 5 mg per week for the first 2 weeks and increase to 10 mg per week for the second 2 weeks and 15 mg per week for the remaining period if tolerated) or the placebo group. Primary outcomes are effusion-synovitis size measured by magnetic resonance imaging (MRI) and knee pain assessed by visual analogue scale (VAS). Secondary outcomes are signal intensity alteration within infrapatellar fat pad (IPFP) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score and subscores, and the Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) responders. Both intention-to-treat and per-protocol analyses will be performed. Discussion If MTX intervention can relieve symptoms and reduce inflammation in patients with mid- to late-stage KOA, it has the potential for significant clinical and public health impact as this low-cost and commonly used intervention would delay the time to knee replacement, leading to substantial cost savings and improve quality of life. Trial registration ClinicalTrials.gov NCT03815448 . Registered on 21 January 2019.

OBJECTIVE:The aim of this study was to investigate cross-sectional associations between serum levels of citrate and knee structural changes and cartilage enzymes in patients with knee osteoarthritis (OA).METHOD:A total of 137 subjects with symptomatic knee OA (mean age 55.0 years, range 34-74, 84% female) were included. Knee radiography was used to assess knee osteophytes, joint space narrowing (JSN) and radiographic OA assessed by Kellgren-Lawrence (K-L) grading system. T2-weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI) was used to determine knee cartilage defects, bone marrow lesions (BMLs) and infrapatellar fat pad (IPFP) signal intensity alternations. Colorimetric fluorescence was used to measure the serum levels of citrate. Enzyme-linked immunosorbent assay was used to measure the serum cartilage enzymes including matrix metalloproteinase (MMP)-3 and MMP-13.RESULTS:After adjustment for potential confounders (age, sex, body mass index), serum citrate was negatively associated with knee osteophytes at the femoral site, cartilage defects at medial femoral site, total cartilage defects, and total BMLs (odds ratio [OR] 0.17-0.30, all P < .05). Meanwhile, serum citrate was negatively associated with IPFP signal intensity alteration (OR 0.30, P = .05) in multivariable analyses. Serum citrate was significantly and negatively associated with MMP-13 (β -3106.37, P < .05) after adjustment for potential confounders. However, citrate was not significantly associated with MMP-3 in patients with knee OA.CONCLUSION:Serum citrate was negatively associated with knee structural changes including femoral osteophytes, cartilage defects, and BMLs and also serum MMP-13 in patients with knee OA, suggesting that low serum citrate may be a potential indicator for advanced knee OA.

To investigate the cross-sectional associations between suprapatellar pouch effusion-synovitis and serum levels of cartilage oligomeric matrix protein (COMP), high sensitivity C-reaction protein (hs-CRP), knee symptom, and structural changes in patients with symptomatic knee osteoarthritis (OA).

目的 探讨膝骨关节炎(osteoarthritis,OA)患者正常范围血清尿酸(uric acid,UA)水平与膝关节症状、结构改变之间的相关性.方法 收集205例膝OA患者,根据纳入及排除标准,最终122例OA患者纳入研究,调查患者一般情况,WOMAC骨关节炎指数(western ontario and mcMaster universities osteoarthritis index,WOMAC)评分评估膝关节症状严重程度,Kellgren-Lawrenc(K-L)分级评估膝关节放射学严重程度,在磁共振成像(magnetic resonance imaging,MRI)上利用Osirix软件测量关节结构改变,过氧化物酶法测定血清UA水平,选取正常范围UA纳入研究,分析UA水平与膝关节症状、结构改变之间的关系.结果 研究发现,以UA中位数(263 μmol/L)分组进行组间比较,与UA ≥263μmol/L组相比,UA＜ 263 μmol/L组患者的身高、体重较小,女性较多,而K-L分级≥2的比例较低;调整性别、年龄及体质指数后,UA水平与WOMAC总分(β=-16.15,P=0.018)、WOMAC疼痛(β=-3.15,P=0.037)、WOMAC僵硬(β=-1.65,P=0.025)呈负相关;但UA水平与膝关节结构改变无明显相关性.结论 在膝OA患者中,正常UA水平与关节症状严重程度呈负相关,提示正常水平UA可能对OA关节症状具有保护作用.

目的 探讨膝骨关节炎(OA)患者血清褪黑素(MT)水平和关节结构及血清标志物之间的相关性.方法 入组169例膝OA患者,对患者一般情况进行问卷调查,使用磁共振对患者膝关节进行摄片,利用Osirix软件测量膝关节软骨体积,并对关节软骨缺损、软骨下骨髓损害进行评级.使用ELISA法测定患者血清MT、基质金属蛋白酶(MMP)-3、MMP-10、MMP-13、白介素(IL)-6、IL-8、肿瘤坏死因子-α(TNF-α)、瘦素、抵抗素和脂联素水平.采用SPSS软件多元回归方法分析血清MT水平与膝OA关节结构及血清标志物的相关性.结果 ①将患者以MT中位数(0.91 ng/ml)水平分为两组,两组间性别、年龄、身体质量指数、关节软骨体积、关节软骨缺损、软骨下骨髓损害和血清IL-8、瘦素、脂联素、MMP-10及MMP-13水平差异均无统计学意义.在MT高水平组中,患者血清MMP-3水平更低,但血清IL-6、TNF-α和抵抗素水平更高,差异均有统计学意义(P＜0.05);②调整混杂因素(包括性别、年龄和身体质量指数)后,血清MT水平与MMP-3水平呈负相关性(OR=0.55,95％CI:0.37～0.81,P=0.03),血清MT水平与IL-6、TNF-α和瘦素水平呈正相关性(OR=2.05,95％ CI:1.27 ～3.29,P=0.003;OR=2.25,95％ CI:1.40 ～ 3.63,P=0.001;OR=1.59,95％ CI:1.05～2.42,P=0.028),与其他血清标志物无显著相关性;③调整混杂因素后(包括性别、年龄和身体质量指数),血清MT水平和关节软骨体积、关节软骨缺损和软骨下骨髓损害均无显著相关性.结论 血清MT水平与膝OA患者MMP-3水平呈负相关性,与血清IL-6、TNF-α和瘦素水平呈正相关性,与关节结构无相关性.结果 显示MT在膝OA中可能发挥一定作用,但需要进一步临床研究证实.

Objective To determine whether infrapatellar fat pad (IPFP) signal intensity measures are predictive of incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative study. Methods Case knees (n = 355), as defined by incident ROA, were matched 1:1 with control knees, according to sex, age, and radiographic status. T2-weighted magnetic resonance images were assessed at P0 (the visit when incident ROA was observed on a radiograph), P1 (1 year prior to P0), and baseline and used to assess IPFP signal intensity semiautomatically. Conditional logistic regression analyses were performed to assess the risk of incident ROA associated with IPFP signal intensity alteration, after adjustment for covariates. Results The mean age of the participants was 60.2 years, and most (66.7%) were female and overweight (mean body mass index 28.3 kg/m(2)). Baseline IPFP measures including the mean value and standard deviation of IPFP signal intensity, the mean value and standard deviation of IPFP high signal intensity, median and upper quartile values of IPFP high signal intensity, and the clustering effect of high signal intensity were associated with incident knee ROA over 4 years. All P1 IPFP measures were associated with incident ROA after 12 months. All P0 IPFP signal intensity measures were associated with ROA. Conclusion The quantitative segmentation of high signal intensity in the IPFP observed in our study confirms the findings of previous work based on semiquantitative assessment, suggesting the predictive validity of semiquantitative assessment of IPFP high signal intensity. The IPFP high signal intensity alteration could be an important imaging biomarker to predict the occurrence of ROA.

Objective: To investigate cross-sectional associations between serum level of Matrix metalloproteinase (MMP) 13 and knee structural measures and circulating inflammatory factors in patients with symptomatic knee osteoarthritis (OA). Design: A total of 149 subjects with symptomatic knee OA were included. Magnetic resonance imaging was used to measure infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage volume and cartilage defects. Knee radiography was used to assess radiographic OA using the KellgrenLawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors and MMP13. Results: In multivariable analyses, serum MMP13 was negatively associated with cartilage volume at patellar site (beta: -32.94 mm(3) per 10 ng/ml, P < 0.05), and positively associated with cartilage defect at medial femoral site (OR: 1.13 per 10 ng/ml, P < 0.05). Also, MMP13 was positively associated with K-L grading and IPFP signal intensity alteration (OR: 1.14 and 1.15 per 10 ng/ml, respectively, both P < 0.05), and negatively associated with IPFP volume (beta: -0.34 cm(3) per 10 ng/ml, P < 0.05). Furthermore, serum level of adiponectin was negatively associated serum MMP13 quartiles (OR: 0.66 per 10 mg/ml, P < 0.05), and serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-8 and IL-18 were positively associated with serum MMP13 quartiles (ORs: 1.01-1.18 per 10 pg/ml, all P < 0.05). Conclusions: Serum level of MMP13 was associated with knee structural abnormalities as well as serum inflammatory factors. These suggest that systemic MMP13 may play a role in knee OA, and could be regulated by inflammatory factors. (c) 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

OBJECTIVE:Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA); however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. DESIGN:A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. RESULTS:In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (β: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (β: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (β: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (β: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. CONCLUSIONS:Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings.

OBJECTIVE:To investigate whether infrapatellar fat pad (IPFP) signal intensity (SI) alteration predicts the occurrence of knee replacement (KR) in knee osteoarthritis (OA) patients over 5 years. DESIGN:The subjects were selected from Osteoarthritis Initiative (OAI) study. Case knees (n = 127) were defined as those who received KR during 5 years follow-up visit. They were matched by gender, age and radiographic status with control knees (n = 127). We used T2-weighted MR images to measure IPFP SI alteration using a newly developed algorithm in MATLAB. The measurements were assessed at baseline (BL), T0 (the visit just before KR) and 1 year before T0 (T-1). Conditional logistic regression was used to analyse the associations between IPFP SI alterations and the risk of KR. RESULTS:Participants were mostly female (57%), with an average age of 63.7 years old and a mean body mass index (BMI) of 29.5 kg/m2. In multivariable analysis, the standard deviation (SD) of IPFP SI [sDev (IPFP)] and the ratio of high SI region volume to whole IPFP volume [Percentage (H)] measured at BL were significantly associated with increased risks of KR after adjustment for covariates. IPFP SI alterations measured at T-1 including sDev (IPFP), Percentage (H) and clustering effect of high SI [Clustering factor (H)] were significantly associated with higher risks of KR. All measurements were significantly associated with higher risks of KR at T0. CONCLUSIONS:IPFP SI is associated with the occurrence of KR suggesting it may play a role in end-stage knee OA.

目的 探讨膝骨关节炎(OA)患者血糖、血脂与血清标志物的相关性.方法 收集膝OA患者169例.通过酶联免疫吸附法检测血清中反映早期膝OA的生物标志物,包括软骨糖蛋白-39(GP-39)、基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-10(MMP-10)、基质金属蛋白酶-13(MMP-13)、血清Ⅰ型胶原交联C-末端肽(CTXⅠ)和Ⅰ型胶原氨基端末肽(NTX Ⅰ),同时记录血生化检验中的空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、极低密度脂蛋白(VLDL)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)水平.将OA患者按GP-39中位数水平分为两组.结果 两组人群的年龄、性别、BMI、FBG、TC、TG、HDL、VLDL、ApoA1、MMP-3、MMP-13及CTX Ⅰ之间差异无统计学意义.多元回归分析中,FBG、TG及VLDL与GP49呈正相关性(OR=1.745,P=0.030;OR=1.369,P=0.050;OR=7.583,P=0.001);ApoA1与MMP-3、MMP-13呈正相关性(OR=9.747,P＜0.001;OR=11.485,P ＜0.001);TC与MMP-10呈正相关性(OR=1.386,P=0.022);ApoB与CTXⅠ呈正相关性(OR=4.349,P=0.048);VLDL与NTXⅠ呈正相关性(OR=2.656,P=0.045).结论 膝OA患者部分血糖及血脂与血清标志物之间有相关性,提示血糖、血脂可能参与膝OA的发病机制.