Article
Rheumatology
Haruka Tsuchiya, Mineto Ota, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Toyonori Sakata, Yumi Tsuchida, Hiroshi Inui, Jun Hirose, Yuta Kochi, Yuho Kadono, Katsuhiko Shirahige, Sakae Tanaka, Kazuhiko Yamamoto, Keishi Fujio
Summary: Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the synovium, where synovial fibroblasts (SFs) play a major role. This study aimed to understand the genetic contribution to molecular regulatory networks in SFs under inflammatory conditions. Methods: SFs from RA and osteoarthritis (OA) patients were stimulated with various cytokines and immune cell subsets were analyzed. Integrative analyses including mRNA expression, histone modifications, 3D genome architecture, and genetic variations were performed. Results: Unstimulated SFs from RA patients showed differences in transcriptome and epigenome compared to OA SFs. Most responses to stimulations were shared between the diseases. SFs expressed pathogenic genes and chromatin remodeling in activated SFs revealed enrichment of RA risk loci in clusters of enhancers induced by proinflammatory cytokines. A RA risk SNP formed 3D contact with the promoter of a gene related to arthritis, and inhibition of this gene suppressed cytokine and chemokine production in SFs. Conclusions: This study identified potential therapeutic targets associated with genetic risk of RA and established a dynamic landscape of activated SFs.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Rheumatology
Raphael Micheroli, Muriel Elhai, Sam Edalat, Mojca Frank-Bertoncelj, Kristina Buerki, Adrian Ciurea, Lucy MacDonald, Mariola Kurowska-Stolarska, Myles J. Lewis, Katriona Goldmann, Cankut Cubuk, Tadeja Kuret, Oliver Distler, Costantino Pitzalis, Caroline Ospelt
Summary: This study integrated single-cell RNA sequencing data to assess the contribution of synovial fibroblast subsets to synovial pathotypes and clinical characteristics in treatment-naive early arthritis. The findings revealed a previously unexplored association between specific synovial pathologies and subtypes of synovial fibroblasts.
Review
Rheumatology
Tamas Nemeth, Gyorgy Nagy, Thomas Pap
Summary: Fibroblast-like synoviocytes (FLS) are crucial cellular components in the synovial membrane of joints, contributing to normal joint function. However, under inflammatory conditions like rheumatoid arthritis (RA), FLS can become overactive and promote inflammation. Therefore, understanding the role of FLS in RA is essential for disease treatment.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Nutrition & Dietetics
Jiyoung Bae, Yang Yang, Xinyun Xu, Jamie Flaherty, Haley Overby, Kelsey Hildreth, Jiangang Chen, Shu Wang, Ling Zhao
Summary: Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. The study found that naringenin (NAR) can promote adipocyte browning and thermogenesis through the activation of PPARγ.
FRONTIERS IN NUTRITION
(2022)
Review
Biochemistry & Molecular Biology
Weibei Sheng, Qichang Wang, Haotian Qin, Siyang Cao, Yihao Wei, Jian Weng, Fei Yu, Hui Zeng
Summary: Osteoarthritis (OA) is a common degenerative joint disease that is exacerbated by population aging, resulting in a significant economic burden. Current therapies are inadequate, but research on peroxisome proliferator-activated receptors (PPARs) shows promise in slowing OA progression. PPARs have emerged as potential targets for effective OA treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Eva M. L. Philippon, Lisanne J. E. van Rooijen, Fatemeh Khodadust, Jan Piet van Hamburg, Conny J. van der Laken, Sander W. Tas
Summary: A spheroid-based model of RA synovial tissue was developed to mimic the 3D interactions between cells and pro-inflammatory mediators. It can be used to study the pathogenesis of rheumatoid arthritis, examine the effects of specific cell types and signaling pathways, and evaluate the efficacy of novel diagnostic and therapeutic compounds.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Rheumatology
Maximilian Kugler, Mirjam Dellinger, Felix Kartnig, Lena Mueller, Teresa Preglej, Leonhard X. Heinz, Elisabeth Simader, Lisa Goeschl, Stephan E. Puchner, Sebastian Weiss, Lisa E. Shaw, Matthias Farlik, Wolfgang Weninger, Giulio Superti-Furga, Josef S. Smolen, Guenter Steiner, Daniel Aletaha, Hans P. Kiener, Myles J. Lewis, Costantino Pitzalis, Anela Tosevska, Thomas Karonitsch, Michael Bonelli
Summary: Activated FLS play a critical role in synovial tissue remodeling and interaction with immune cells in rheumatoid arthritis (RA). Co-culture experiments demonstrated that cytokine-activated FLS enhance T cell activation, proliferation, and differentiation. Transcriptomic analysis revealed a correlation between FLS cytokine signatures and infiltrating CD4(+) T cells in RA synovial tissue. ICAM1 was identified as an important mediator in TNF-mediated FLS-T cell interaction.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Anil K. Singh, Mahamudul Haque, Bhanupriya Madarampalli, Yuanyuan Shi, Benjamin J. Wildman, Abdul Basit, Sadik A. Khuder, Bhagwat Prasad, Quamarul Hassan, Salahuddin Ahmed, Madhu M. Ouseph
Summary: IL-6 trans-signaling induces molecular reprogramming of RASFs to osteoclast-like cells through the activation of transcription factor Ets2, leading to increased expression of osteoclast-specific proteins and markers of invasive phenotype.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Rheumatology
Li Zheng, Fanlei Hu, Wenjie Bian, Yingni Li, Linqi Zhang, Lianjie Shi, Xiaoxu Ma, Yanying Liu, Xuewu Zhang, Zhanguo Li
Summary: Dkk-1 exacerbates inflammation, cartilage erosion, and angiogenesis mediated by synovial fibroblasts in RA. Modulation of DKK-1 expression may facilitate the development of novel strategies to control RA.
CLINICAL RHEUMATOLOGY
(2021)
Article
Rheumatology
Tadashi Hosoya, Tetsuya Saito, Hiroyuki Baba, Nao Tanaka, Seiji Noda, Youji Komiya, Yasuhiro Tagawa, Akio Yamamoto, Fumitaka Mizoguchi, Kimito Kawahata, Nobuyuki Miyasaka, Hitoshi Kohsaka, Shinsuke Yasuda
Summary: This study reveals that inhibiting CDK4/6 activity can attenuate cartilage destruction and MMP-3 production, providing chondroprotective effects. These effects were achieved by impairing AP-1 transcriptional activity and destabilizing JUN.
Article
Cardiac & Cardiovascular Systems
Shi Fang, M. Christine Livergood, Pablo Nakagawa, Jing Wu, Curt D. Sigmund
Summary: This review focuses on the mechanisms by which nuclear receptors mediate transcriptional responses, with a specific emphasis on the role of PPARγ in regulating blood pressure. Genetic and clinical trial data demonstrate the importance of PPARγ in hypertension, and the tissue- and cell-specific molecular mechanisms by which PPARs modulate blood pressure and related phenotypes are detailed. The role of placental PPARs in preeclampsia is also discussed, along with future research directions and implications for novel therapies.
CIRCULATION RESEARCH
(2021)
Article
Immunology
Chun-Han Hou, Po-Chun Chen, Ju-Fang Liu
Summary: This study provides novel insights into the role of CXCL1 in the pathogenesis of rheumatoid arthritis by promoting COX-II expression to regulate disease progression.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Samuel Kemble, Adam P. Croft
Summary: This review focuses on discussing the disease persistence pathways of rheumatoid arthritis and treating the disease through regulating specific cellular behaviors. The article reveals the heterogeneity of tissue resident synovial cells and how they function in joint inflammation. Finally, specific targeted therapeutic strategies against pathogenic subsets of fibroblasts in RA are proposed.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Nasim Dana, Gordon A. Ferns, Reza Nedaeinia, Shaghayegh Haghjooy Javanmard
Summary: Obesity affects tumor development and interacts with leptin and peroxisome proliferator-activated receptors. Studies have shown an association between obesity and various types of cancer, including breast cancer.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)
Review
Medicine, General & Internal
Katharina Knab, David Chambers, Gerhard Kroenke
Summary: This review summarizes the phenotypic and molecular characteristics of immune-regulatory macrophages and fibroblasts in the synovial tissue, and highlights their crosstalk during joint homeostasis and joint inflammation, which is vital to understand the molecular basis of prevalent inflammatory joint diseases such as rheumatoid arthritis.
FRONTIERS IN MEDICINE
(2022)
Article
Orthopedics
E. Charlier, O. Malaise, M. Zeddou, S. Neuville, G. Cobraiville, C. Deroyer, C. Sanchez, P. Gillet, W. Kurth, D. de Seny, B. Relic, M. G. Malaise
OSTEOARTHRITIS AND CARTILAGE
(2016)
Article
Oncology
Rachel Henkens, Philippe Delvenne, Mohammad Arafa, Michel Moutschen, Mustapha Zeddou, Lutz Tautz, Jacques Boniver, Tomas Mustelin, Souad Rahmouni
Article
Cell Biology
Mustapha Zeddou, Alexandra Briquet, Biserka Relic, Claire Josse, Michel G. Malaise, Andre Gothot, Chantal Lechanteur, Yves Beguin
CELL BIOLOGY INTERNATIONAL
(2010)
Article
Cell & Tissue Engineering
Alexandra Briquet, Celine Gregoire, Fanny Comblain, Laurence Servais, Mustapha Zeddou, Chantal Lechanteur, Yves Beguin
Article
Pathology
Mustapha Mouallif, Adelin Albert, Mustapha Zeddou, My Mustapha Ennaji, Philippe Delvenne, Samuel Guenin
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
(2014)
Article
Rheumatology
Olivier Malaise, Biserka Relic, Florence Quesada-Calvo, Edith Charlier, Mustapha Zeddou, Sophie Neuville, Philippe Gillet, Edouard Louis, Dominique de Seny, Michel G. Malaise
Article
Cell & Tissue Engineering
Mustapha Zeddou, Biserka Relic, Olivier Malaise, Edith Charlier, Aline Desoroux, Yves Beguin, Dominique de Seny, Michel G. Malaise
STEM CELLS AND DEVELOPMENT
(2012)
Review
Integrative & Complementary Medicine
Mustapha Zeddou
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2019)
Article
Rheumatology
Olivier Malaise, Biserka Relic, Edith Charlier, Mustapha Zeddou, Sophie Neuville, Celine Deroyer, Philippe Gillet, Edouard Louis, Michel G. Malaise, Dominique de Seny
ARTHRITIS RESEARCH & THERAPY
(2016)
Article
Virology
Mustapha Zeddou, Souad Rahmouni, Arnaud Vandamme, Nathalie Jacobs, Frederic Frippiat, Philippe Leonard, Nicole Schaaf-Lafontaine, Dolores Vaira, Jacques Boniver, Michel Moutschen
Article
Pharmacology & Pharmacy
M Zeddou, R Greimers, N de Valensart, B Nayjib, K Tasken, J Boniver, M Moutschen, S Rahmouni
BIOCHEMICAL PHARMACOLOGY
(2005)
Article
Biochemistry & Molecular Biology
S Rahmouni, EM Aandahl, B Nayjib, M Zeddou, S Giannini, M Verlaet, R Greimers, J Boniver, K Tasken, M Moutschen
BIOCHEMICAL JOURNAL
(2004)
Article
Medicine, Research & Experimental
Marijn A. Scheijde-Vermeulen, Lennart A. Kester, Liset Westera, Bastiaan B. J. Tops, Friederike A. G. Meyer-Wentrup
Summary: This study aimed to evaluate the feasibility of integrating state-of-the-art sequencing techniques and flow cytometry into the diagnostic workup of pediatric lymphoma. The results showed that this integration is not only feasible but also provides additional diagnostic information.
LABORATORY INVESTIGATION
(2024)
Article
Medicine, Research & Experimental
Enrico Berrino, Sara Erika Bellomo, Anita Chesta, Paolo Detillo, Alberto Bragoni, Amedeo Gagliardi, Alessio Naccarati, Matteo Cereda, Gianluca Witel, Anna Sapino, Benedetta Bussolati, Gianni Bussolati, Caterina Marchi
Summary: Formalin-fixed paraffin-embedded (FFPE) samples are crucial for tissue-based analysis in precision medicine, but the quality of these samples can affect the reliability of sequencing data. The use of acid-deprived fixatives guarantees the highest DNA preservation and sequencing performance, enabling more complex molecular profiling of tissue samples.
LABORATORY INVESTIGATION
(2024)
Article
Medicine, Research & Experimental
Roope A. Kallionpaa, Sirkku Peltonen, Kim My Le, Eija Martikkala, Mira Jaaskelainen, Elnaz Fazeli, Pilvi Riihila, Pekka Haapaniemi, Anne Rokka, Marko Salmi, Ilmo Leivo, Juha Peltonen
Summary: This study investigated the immune microenvironment of cutaneous neurofibromas (cNFs) in patients with neurofibromatosis 1 (NF1). The results showed that cNFs have substantial populations of T cells and macrophages, which may be tumor-specific. T cell populations in cNFs were found to be different from those in the skin, and cNFs exhibited lower expression of proteins related to T cell-mediated immunity compared to the skin.
LABORATORY INVESTIGATION
(2024)