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      Association of autoimmune diseases with the occurrence of osteoarthritis: a gene expression and Mendelian randomization study

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          Abstract

          Background

          Observational studies have indicated a potential association between autoimmune diseases and the occurrence of Osteoarthritis (OA), with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.

          Methods

          In the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for OA were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and OA. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and OA. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as of OA using a real-world database (the MIMIC-IV database). Based on public gene expression sequencing data, we further explored the potential shared pathogenesis between autoimmune diseases and OA.

          Results

          In our univariable MR study, we identified five autoimmune diseases that are associated with OA. These include Celiac disease (OR = 1.061, 95% CI = 1.018–1.105, p = 0.005), Crohn’s disease (OR = 1.235, 95% CI = 1.149–1.327, p = 9.44E-09), Ankylosing spondylitis (OR = 2.63, 95% CI = 1.21–5.717, p = 0.015), RA (OR = 1.082, 95% CI = 1.034–1.133, p = 0.001), and Ulcerative colitis (OR = 1.175, 95% CI = 1.068–1.294, p = 0.001). In the mediation effect analysis, it was found that there is no correlation between cytokines and autoimmune diseases and OA. Based on transcriptome data analysis, it was found that metabolism-related pathways play a key role in the co-morbidity of autoimmune diseases and OA.

          Conclusion

          Our findings revealed that genes associated with Celiac disease, Crohn’s disease, Ankylosing spondylitis, RA, and Ulcerative colitis were independently linked to the development of OA. Furthermore, we conducted an analysis of potential pathogenic genes between these diseases and OA, offering a novel approach for the simultaneous treatment of multiple conditions.

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          Most cited references29

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          Zooming in and Out of Programmed Cell Death in Osteoarthritis: A Scientometric and Visualized Analysis

          Abstract During the past decade, mounting evidence has increasingly linked programmed cell death (PCD) to the progression and development of osteoarthritis (OA). There is a significant need for a thorough scientometric analysis that recapitulates the relationship between PCD and OA. This study aimed to collect articles and reviews focusing on PCD in OA, extracting data from January 1st, 2013, to October 31st, 2023, using the Web of Science. Various tools, including VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package, were employed for scientometric and visualization analyses. Notably, China, the USA, and South Korea emerged as major contributors, collectively responsible for more than 85% of published papers and significantly influencing research in this field. Among different institutions, Shanghai Jiao Tong University, Xi’an Jiao Tong University, and Zhejiang University exhibited the highest productivity. Prolific authors included Wang Wei, Wang Jing, and Zhang Li. Osteoarthritis and Cartilage had the most publications in this area. Keywords related to PCD in OA prominently highlighted ‘chondrocytes’, ‘inflammation’, and ‘oxidative stress’, recognized as pivotal mechanisms contributing to PCD within OA. This study presents the first comprehensive scientometric analysis, offering a broad perspective on the knowledge framework and evolving patterns concerning PCD in relation to OA over the last decade. Such insights can aid researchers in comprehensively understanding this field and provide valuable directions for future explorations.
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            Intra-Articular Application of Autologous, Fat-Derived Orthobiologics in the Treatment of Knee Osteoarthritis: A Systematic Review.

            The aim of this study was to review the current literature regarding the effects of intra-articularly applied, fat-derived orthobiologics (FDO) in the treatment of primary knee osteoarthritis over a mid-term follow-up period. A systematic literature search was conducted on the online databases of Scopus, PubMed, Ovid MEDLINE, and Cochrane Library. Studies investigating intra-articularly applied FDO with a minimum number of 10 knee osteoarthritis patients, a follow-up period of at least 2 years, and at least 1 reported functional parameter (pain level or Patient-Reported Outcome Measures) were included. Exclusion criteria encompassed focal chondral defects and techniques including additional arthroscopic bone marrow stimulation. In 28 of 29 studies, FDO showed a subjective improvement in symptoms (pain and Patient-Reported Outcome Measures) up to a maximum follow-up of 7.2 years. Radiographic cartilage regeneration up to 3 years postoperatively, as well as macroscopic cartilage regeneration investigated via second-look arthroscopy, may corroborate the favorable clinical findings in patients with knee osteoarthritis. The methodological heterogeneity in FDO treatments leads to variations in cell composition and represents a limitation in the current state of knowledge. However, this systematic review suggests that FDO injection leads to beneficial mid-term results including symptom reduction and preservation of the affected joint in knee osteoarthritis patients.
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              Musculoskeletal mimics of lumbosacral radiculopathy

              Electrodiagnostic evaluations are commonly requested for patients with suspected radiculopathy. Understanding lower extremity musculoskeletal conditions is essential for electrodiagnostic medicine specialists, as musculoskeletal disorders often mimic or coexist with radiculopathy. This review delineates radicular pain from other types originating from the lumbosacral spine and describes musculoskeletal conditions frequently mimicking radiculopathy, such as those that cause radiating pain and sensorimotor dysfunction. In clinical evaluation, a history of pain radiating along a specific dermatomal territory with associated sensory disturbance suggests radiculopathy. Physical examination findings consistent with radiculopathy include myotomal weakness, depressed or absent muscle stretch reflexes, focal atrophy along a discrete nerve root territory, and potentially positive dural tension maneuvers like the straight leg raise. However, electrodiagnostic medicine specialists must be knowledgeable of musculoskeletal mimics, which may manifest as incomplete radiation within or beyond a dermatomal territory, non‐radiating pain, tenderness, and give‐way weakness, in the context of a normal neurological examination. A systematic approach to musculoskeletal examination is vital, and this review focuses on high‐yield physical examination maneuvers and diagnostic investigations to differentiate between musculoskeletal conditions and radiculopathy. This approach ensures accurate diagnoses, promotes resource stewardship, enhances patient satisfaction, and optimizes care delivery. Musculoskeletal conditions resembling L1 to S4 radiculopathy are reviewed, emphasizing their distinctive features in history, physical examination, and diagnostic investigation. Among the more than 30 musculoskeletal disorders reviewed are hip and knee osteoarthritis, lumbar facet syndrome, myofascial pain syndrome, greater trochanteric pain syndrome, and plantar fasciitis.
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                Author and article information

                Contributors
                Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2745500/overviewRole: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role: Role: Role:
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                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                05 September 2024
                2024
                : 11
                : 1435312
                Affiliations
                Department of Sports Medicine and Rehabilitation, Affiliated Sport Hospital of CDSU , Chengdu, China
                Author notes

                Edited by: Yao Lu, Southern Medical University, China

                Reviewed by: Weizhong Qi, Southern Medical University, China

                Yun Ji, China Agricultural University, China

                Maytham T. Qasim, Al-Ayen University, Iraq

                *Correspondence: Jing Dan, 287230773@ 123456qq.com ; Huai Min Lu, ctfy1958ydyxkf@ 123456163.com
                Article
                10.3389/fmed.2024.1435312
                11412204
                39301493
                759946d4-ac44-44a2-ba89-69aff17ee796
                Copyright © 2024 Dan, Lu, Zhou, Wang and Wang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 May 2024
                : 20 August 2024
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 29, Pages: 9, Words: 5345
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Clinical Innovation Project of the Affiliated Sports Hospital of Chengdu Sport University (Project no. LCCX22C04).
                Categories
                Medicine
                Original Research
                Custom metadata
                Rheumatology

                osteoarthritis (oa),autoimmune diseases,mendelian randomization (mr),genome-wide association study (gwas),metabolism-related

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