Article
Endocrinology & Metabolism
Xianwen Liu, Xinping Li, Bingqiang Hua, Xiaoqin Yang, Junfa Zheng, Shuguang Liu
Summary: The study revealed that WNT16 plays a crucial role in the early stage of TMJOA by regulating cartilage anabolic and catabolic factors to protect against inflammatory responses. It may serve as a potential novel therapeutic target for TMJOA.
Article
Pharmacology & Pharmacy
Xiaopeng Song, Tianwen Ma, Hailong Hu, Mingchao Zhao, Hui Bai, Xinyu Wang, Lin Liu, Ting Li, Xuanbo Sheng, Xinyu Xu, Xinmin Zhang, Li Gao
Summary: Chronic circadian rhythm disturbance can lead to osteoarthritis-like pathological changes in knee cartilage of rats, accelerating cartilage matrix degradation and synovial inflammation. This disruption is associated with the activation of the canonical Wnt/beta-catenin signaling pathway, affecting the balance of matrix synthesis and catabolic metabolism in cartilage and chondrocytes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Wenhan Wang, Jiazhi Duan, Wenjun Ma, Bowei Xia, Feng Liu, Ying Kong, Boyan Li, Hang Zhao, Liang Wang, Keyi Li, Yiwei Li, Xiheng Lu, Zhichao Feng, Yuanhua Sang, Gang Li, Hao Xue, Jichuan Qiu, Hong Liu
Summary: Osteoarthritis is a leading cause of movement disorders in humans, and oxidative stress-induced metabolic imbalance in chondrocytes plays a crucial role in its occurrence and development. In this study, a trimanganese tetroxide nanozyme was designed to reduce oxidative stress-induced damage and its therapeutic effect was investigated. The nanozyme successfully restored metabolic balance and controlled inflammation in chondrocytes, and when incorporated into a cross-linked chondroitin sulfate hydrogel, it effectively treated osteoarthritis in mouse models. These findings suggest that the Mn3O4@CS hydrogel could be a potentially effective therapeutic treatment for osteoarthritis.
Article
Pharmacology & Pharmacy
Liang He, Ziwei Xu, Xin Niu, Rong Li, Fanhua Wang, Yu You, Jingduo Gao, Lei Zhao, Karan M. Shah, Jian Fan, Mingyao Liu, Jian Luo
Summary: This study reveals that GPRC5B can inhibit cartilage degradation, promote cartilage regeneration, and protect against osteoarthritis. The findings were validated in vitro experiments and a mouse model, and the study also identified the regulatory role of the AKT-mTOR-autophagy signaling pathway.
ACTA PHARMACEUTICA SINICA B
(2023)
Review
Endocrinology & Metabolism
Xiaoping Ye, Xianwen Liu
Summary: Wnt16, a member of the Wnt family, plays an important role in bone density, bone strength, and osteoarthritis. Recent studies have shown that Wnt16 acts as a positive regulator of bone mass and a protective regulator of osteoarthritis progression, and the mechanisms of its signaling have been illustrated.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Integrative & Complementary Medicine
Yiming Xu, Song Xue, Tian Zhang, Xinmeng Jin, Cong Wang, Haiming Lu, Yiming Zhong, Hongjie Chen, Libo Zhu, Jinzhong Ma, Weilin Sang
Summary: This study found that Toddalolactone (TOD) can inhibit inflammation and the expression of catabolic mediators in inflammatory chondrocytes in vitro, as well as inhibit RANKL-induced osteoclast differentiation. The study also confirmed that TOD can suppress articular cartilage destruction and bone resorption by inhibiting the activation of NF-kappa B and MAPK signaling pathways. In an ACLT mouse model, TOD was found to reduce cartilage erosion and bone resorption.
Article
Medicine, Research & Experimental
Hailong Hu, Xiaopeng Song, Yue Li, Tianwen Ma, Hui Bai, Mingchao Zhao, Xinyu Wang, Lin Liu, Li Gao
Summary: The study showed that emodin effectively reduced the expression of MMP-3, MMP-13, ADAMTS-4, and iNOS in chondrocytes and cartilage, protected knee joint cartilage, and significantly decreased blood levels of COX-2 and PGE2. Emodin at 5 μmol/L was found to be the best concentration for treating chondrocytes, while emodin at 80 mg/kg had a protective effect comparable to Celecoxib.
Article
Pharmacology & Pharmacy
Fanhua Wang, Lu Ma, Yi Ding, Liang He, Mingzhi Chang, Yingquan Shan, Stefan Siwko, Geng Chen, Yuwei Liu, Yunyun Jin, Xiaochun Peng, Jian Luo
Summary: The study identified Gpr84 as the receptor for medium-chain fatty acids in chondrocytes, showing that deficiency of Gpr84 exacerbated cartilage degradation in OA pathogenesis. Activation of Gpr84 enhanced cartilage extracellular matrix generation and protected against OA degeneration, without severe cartilaginous side effects.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Bingqiang Hua, Jin Qiu, Xiaoping Ye, Xianwen Liu
Summary: Studies have shown that SM04690 may promote FCSCs chondrogenesis and repair TMJ cartilage, highlighting its therapeutic potential in TMJOA.
Review
Pathology
Amandeep Kaur Gill, Peter J. McCormick, David Sochart, Giovanna Nalesso
Summary: Degradation of the articular cartilage is a characteristic of osteoarthritis, which is a progressive and chronic musculoskeletal disease affecting millions of people worldwide. Among the various signalling pathways involved in disease development, the Wnt signalling plays a crucial role in maintaining tissue homeostasis. It is increasingly evident that a balanced activation of the Wnt signalling is necessary to prevent degenerative mechanisms. This review summarizes our current understanding of how the Wnt signalling is regulated in the articular cartilage, with a particular emphasis on receptor-mediated mechanisms.
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
(2023)
Review
Cell Biology
Xinyan Li, Yuanyuan Han, Guimiao Li, Yingze Zhang, Juan Wang, Chen Feng
Summary: This review summarizes the role of Wnt signaling pathways in joint development and cartilage maintenance, with a focus on aberrant mechanical loading and inflammation as major contributors to osteoarthritis progression. Additionally, emerging Wnt-related modulators and treatments targeting Wnt signaling are discussed, providing valuable insights for diagnosing and treating osteoarthritis and other degenerative joint diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Developmental Biology
Daniel B. Dranow, Pierre Le Pabic, Thomas F. Schilling
Summary: Non-canonical/beta-catenin-independent Wnt signaling is crucial for tissue/cell polarity in epithelia, but its role in mesenchymal tissues like the skeleton is not well studied. Mutations in non-canonical Wnt signaling pathway genes cause skeletal diseases in humans, disrupting bone growth. Ror2 is a non-canonical Wnt receptor/co-receptor. Zebrafish with ror2-/- mutation show craniofacial skeletal defects and chondrocyte polarity disruptions. The proline-rich domain of Ror2 is required for its function in rescuing the defects.
Article
Multidisciplinary Sciences
Tazio Maleitzke, Alexander Hildebrandt, Tamara Dietrich, Jessika Appelt, Denise Jahn, Ellen Otto, Dario Zocholl, Anke Baranowsky, Georg N. Duda, Serafeim Tsitsilonis, Johannes Keller
Summary: Calcitonin has potential protective effects against joint inflammation, cartilage degradation, and excessive bone remodeling in experimental RA.
Article
Orthopedics
C. Cherifi, A. Latourte, S. Vettorazzi, J. Tuckermann, S. Provot, H. -K. Ea, A. Ledoux, J. Casas, O. Cuvillier, P. Richette, A. Ostertag, E. Hay, M. Cohen-Solal
Summary: The osteoclast secretome promotes chondrocyte catabolism by increasing expression of Mmp3 and Mmp13 and activating the JNK signaling pathway, leading to matrix degradation. Inhibition of osteoclast-mediated chondrocyte catabolism with JTE013 protects against OA, indicating that osteoclastic S1P contributes to cartilage damage. S1P is identified as a potential therapeutic target in OA.
OSTEOARTHRITIS AND CARTILAGE
(2021)
Article
Biology
Subburaman Mohan, Shelia Pourteymoor, Chandrasekhar Kesavan
Summary: This study examined the expression and biological effects of WNT16 in mouse articular chondrocytes (ACs), and found that WNT16 promotes AC proliferation and increases the expression of immature chondrocyte markers while inhibiting the expression of mature chondrocyte markers. The results suggest that WNT16 regulates joint cartilage homeostasis in ACs through its direct effect and modulation of other Wnt ligands.
Article
Cell Biology
Rita Silva-Gomes, Sarah N. Mapelli, Marie-Astrid Boutet, Irene Mattiola, Marina Sironi, Fabio Grizzi, Federico Colombo, Domenico Supino, Silvia Carnevale, Fabio Pasqualini, Matteo Stravalaci, Remi Porte, Andrea Gianatti, Constantino Pitzalis, Massimo Locati, Maria Jose Oliveira, Barbara Bottazzi, Alberto Mantovani
Summary: The MS4A gene family encodes 18 tetraspanin-like proteins, most of which have unknown functions. Some members such as MS4A1, MS4A2, MS4A3, and MS4A4A have important roles in immunity. The differential expression and regulation of MS4A family members during myelomonocytic differentiation suggest their potential value as therapeutic targets.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Rheumatology
Christian Dejaco, Pedro M. Machado, Francesco Carubbi, Philipp Bosch, Lene Terslev, Giorgio Tamborrini, Luca Maria Sconfienza, Carlo Alberto Scire, Sebastian Ruetten, Jef van Rompay, Fabian Proft, Costantino Pitzalis, Marina Obradov, Rikke Helene Moe, Vasco V. Mascarenhas, Clara Malattia, Andrea Sabine Klauser, Alison Kent, Lennart Jans, Wolfgang Hartung, Hilde Berner Hammer, Christina Duftner, Peter Balint, Alessia Alunno, Xenofon Baraliakos
Summary: This study developed evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatologic and musculoskeletal diseases. Recommendations included preference for imaging over palpation to guide targeted interventions at peripheral joints, periarticular musculoskeletal structures, nerves and the spine, with ultrasound as the favored imaging technique for peripheral joints and nerves.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Asif J. Iqbal, Franziska Krautter, Isobel A. Blacksell, Rachael D. Wright, Shani N. Austin-Williams, Mathieu-Benoit Voisin, Mohammed T. Hussain, Hannah L. Law, Toshiro Niki, Mitsuomi Hirashima, Michele Bombardieri, Costantino Pitzalis, Alok Tiwari, Gerard B. Nash, Lucy Norling, Dianne Cooper
Summary: This study investigates the role of immunomodulatory lectin Galectin-9 (Gal-9) in neutrophil recruitment. The results show that Gal-9 is upregulated in inflamed blood vessels and released by activated endothelial cells. Gal-9 binding induces neutrophil activation and can enhance their interaction with endothelial cells. Both soluble and immobilized Gal-9 function as adhesion molecules and can capture neutrophils. These findings provide insights into the importance of Gal-9 in leukocyte recruitment during inflammation.
Article
Multidisciplinary Sciences
John D. Isaacs, Sarah Brockbank, Ayako Wakatsuki Pedersen, Catharien Hilkens, Amy Anderson, Philip Stocks, Dennis Lendrem, Jessica Tarn, Graham R. Smith, Ben Allen, John Casement, Julie Diboll, Rachel Harry, Faye A. H. Cooles, Andrew P. Cope, Gemma Simpson, Ruth Toward, Hayley Noble, Angela Parke, Wing Wu, Fiona Clarke, David Scott, Ian C. Scott, James Galloway, Heidi Lempp, Fowzia Ibrahim, Samana Schwank, Gemma Molyneux, Tomi Lazarov, Frederic Geissmann, Carl S. Goodyear, Iain B. McInnes, Iona Donnelly, Ashley Gilmour, Aysin Tulunay Virlan, Duncan Porter, Frederique Ponchel, Paul Emery, Jehan El-Jawhari, Rekha Parmar, Michael F. McDermott, Benjamin A. Fisher, Steve P. Young, Philip Jones, Karim Raza, Andrew Filer, Costantino Pitzalis, Michael R. Barnes, David S. Watson, Rafael Henkin, Georgina Thorborn, Liliane Fossati-Jimack, Stephen Kelly, Frances Humby, Michele Bombardieri, Sharmila Rana, Zhilong Jia, Katriona Goldmann, Myles Lewis, Sandra Ng, Adriano Barbosa-Silva, Evan Tzanis, Amaya Gallagher-Syed, Christopher R. John, Michael R. Ehrenstein, Gioia Altobelli, Sandra Martins, Dao Nguyen, Humayara Ali, Coziana Ciurtin, Maya Buch, Deborah Symmons, Jane Worthington, Ian N. Bruce, Jamie C. Sergeant, Suzanne M. M. Verstappen, Fiona Stirling, Adwoa Hughes-Morley, Brian Tom, Vernon Farewell, Yujie Zhong, Peter C. Taylor, Christopher D. Buckley, Sarah Keidel, Carolyn Cuff, Marc Levesque, Andrew Long, Zheng Liu, Samantha Lipsky, Bohdan Harvey, Michael Macoritto, Feng Hong, Sukru Kaymakcalan, Wayne Tsuji, Tony Sabin, Neil Ward, Susan Talbot, Desmond Padhji, Matthew Sleeman, Donna Finch, Athula Herath, Catharina Lindholm, Martin Jenkins, Meilien Ho, Sally Hollis, Chris Marshall, Gerry Parker, Matt Page, Hannah Edwards, Alexandru Cuza, Neil Gozzard, Ioannis Pandis, Anthony Rowe, Francisco Bonachela Capdevila, Matthew J. Loza, Mark Curran, Denny Verbeeck, Dan Baker, Christopher M. Mela, Ivana Vranic, Catherine T. Mela, Stephen Wright, Lucy Rowell, Emma Vernon, Nina Joseph, Neil Payne, Ravi Rao, Michael Binks, Alexandra Belson, Valerie Ludbrook, Kirsty Hicks, Hannah Tipney, Joanne Ellis, Samiul Hasan, Arnaud Didierlaurent, Wivine Burny, Andrea Haynes, Chris Larminie, Ray Harris, Daniela Dastros-Pitei, Claudio Carini, Blerina Kola, Scott Jelinsky, Martin Hodge, Mateusz Maciejewski, Daniel Ziemek, Peter Schulz-Knappe, Hans-Dieter Zucht, Petra Budde, Mark Coles, James A. Butler, Simon Read
Summary: This study conducted comprehensive clinical and molecular profiling of early, drug naive RA patients, establishing a high-quality sample biobank and performing multi-omic immune phenotyping. The data obtained is expected to provide important insights into the pathogenesis, progression, and therapeutic response of RA.
Article
Medicine, General & Internal
Kimberly Pistorius, Lucy Ly, Patricia R. Souza, Esteban A. Gomez, Duco S. Koenis, Ana R. Rodriguez, Julie Foster, Jane Sosabowski, Mark Hopkinson, Vinothini Rajeeve, Bernd W. Spur, Andrew Pitsillides, Costantino Pitzalis, Jesmond Dalli
Summary: In patients with rheumatoid arthritis, the concentration of MCTR3 in plasma is negatively correlated with joint disease activity and severity. Research shows that MCTR3 can confer enduring joint protective properties by reprogramming monocytes and its anti-arthritic and tissue reparative activities are mediated in part by Arg-1.
Article
Rheumatology
Faye A. H. Cooles, Jessica Tarn, Dennis W. Lendrem, Najib Naamane, Chung M. A. Lin, Ben Millar, Nicola J. Maney, Amy E. Anderson, Nishanthi Thalayasingam, Julie Diboll, Vincent Bondet, Darragh Duffy, Michael R. Barnes, Graham R. Smith, Sandra Ng, David Watson, Rafael Henkin, Andrew P. Cope, Louise N. Reynard, Arthur G. Pratt, John D. Isaacs
Summary: The interferon gene signature (IGS) in early, treatment naive rheumatoid arthritis (eRA) patients can negatively affect initial treatment response by causing sustained, epigenetically mediated increases in lymphocyte activation and proliferation. This highlights the importance of the IGS as a prognostic biomarker and suggests the rationale for targeting IFN-alpha in selected eRA patients.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Jing Wang, Donna Conlon, Felice Rivellese, Alessandra Nerviani, Myles J. Lewis, William Housley, Marc C. Levesque, Xiaohong Cao, Carolyn Cuff, Andrew Long, Costantino Pitzalis, Melanie C. Ruzek
Summary: This study aimed to understand the mechanisms of response to anti-TNF therapies in rheumatoid arthritis (RA) patients. The researchers analyzed RNA sequencing data from synovial tissue before and after treatment and measured serum proteins encoded by differentially expressed synovial genes. The results showed that patients with a good response to anti-TNF therapy had elevated immune pathways at baseline, which were down-regulated after treatment. These findings contribute to understanding patient responsiveness to anti-TNF treatment and suggest the potential for developing predictive markers of treatment response and early treatment options.
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Rheumatology
Anja Meyer, Ryan E. Sienes, Wes Nijim, Brian Zanotti, Sadiq Umar, Michael V. Volin, Katrien Van Raemdonck, Myles Lewis, Costantino Pitzalis, Shiva Arami, Mina Al-Awqati, Huan J. Chang, Pim Jetanalin, Georg Schett, Nadera Sweiss, Shiva Shahrara
Summary: The study found that syntenin-1 is enriched in rheumatoid arthritis (RA) specimens compared to osteoarthritis synovial fluid and normal synovial tissue. However, the cellular origin, immunoregulation and molecular mechanism of syntenin-1 in RA are still unknown.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Editorial Material
Rheumatology
Myles J. Lewis, Costantino Pitzalis
Summary: In 2022, significant progress was made in predicting treatment response in rheumatoid arthritis. This was achieved through gene-expression profiling in synovial biopsy samples, assessment of interferon-response genes in the blood, and the application of machine learning to patients' clinical parameters and genetic variance.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Review
Pathology
Amandeep Kaur Gill, Peter J. McCormick, David Sochart, Giovanna Nalesso
Summary: Degradation of the articular cartilage is a characteristic of osteoarthritis, which is a progressive and chronic musculoskeletal disease affecting millions of people worldwide. Among the various signalling pathways involved in disease development, the Wnt signalling plays a crucial role in maintaining tissue homeostasis. It is increasingly evident that a balanced activation of the Wnt signalling is necessary to prevent degenerative mechanisms. This review summarizes our current understanding of how the Wnt signalling is regulated in the articular cartilage, with a particular emphasis on receptor-mediated mechanisms.
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Nathalie Ringstrom, Charlotte Edling, Giovanna Nalesso, Kamalan Jeevaratnam
Summary: The extracellular matrix (ECM) of the heart plays a crucial role in various pathological conditions, and the aging process itself brings about changes in the heart, increasing the risk of abnormal heart rhythm. The proteomic composition of the ECM and its changes with age are yet to be fully understood. Limited research progress in this field is mainly due to the challenges in unraveling the tightly bound cardiac proteomic components and the dependence on time-consuming and costly animal models. This review provides an overview of the cardiac ECM composition, the role of different components in the healthy heart, ECM remodeling, and its effects with aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Cintia Scucuglia Heluany, Anna De Palma, Nicholas James Day, Sandra Helena Poliselli Farsky, Giovanna Nalesso
Summary: Exposure to hydroquinone, a benzene metabolite found in motor fuels and cigarette smoke, exacerbates synovial hypertrophy and oxidative stress in the synovium and aggravates cartilage damage in a rat model of inflammatory arthritis induced by collagen type II injection. Hydroquinone downregulates SOX-9 and Col2a1 genes, upregulates MMP-3 and ADAMTS5 genes, reduces proteoglycan content, and promotes oxidative stress in articular chondrocytes. The harmful effects of hydroquinone on articular cartilage health are mediated by the activation of the Aryl Hydrocarbon Receptor.
Review
Biochemistry & Molecular Biology
Susan Siyu Wang, Myles J. Lewis, Costantino Pitzalis
Summary: Rheumatoid arthritis (RA) is a complex disease with heterogeneity in disease severity and treatment response. Current prediction methods for treatment response have limitations, and genetics and environmental factors alone cannot fully explain the differences between patients. Recent studies have shown that DNA methylation plays a role in the pathogenesis and progression of RA, and specific DNA methylation profiles in the blood may serve as predictive biomarkers. This review examines the evidence for DNA methylation signatures in treatment response and discusses the potential for future progress in this area.
Article
Rheumatology
Katriona Goldmann, Athina Spiliopoulou, Andrii Iakovliev, Darren Plant, Nisha Nair, Cankut Cubuk, Paul McKeigue, Michael R. Barnes, Anne Barton, Costantino Pitzalis, Myles J. Lewis
Summary: This study conducted expression quantitative trait locus (eQTL) analysis using RNA-Sequencing to explore the link between genetic variants and gene expression in rheumatoid arthritis (RA) patients. The analysis identified 898 eQTL genes in synovium and blood, with 232 genes in common. A specific eQTL at HLA-DPB2 was found to be associated with clinical severity and the lympho-myeloid pathotype.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Elisabetta Sciacca, Anna E. A. Surace, Salvatore Alaimo, Alfredo Pulvirenti, Felice Rivellese, Katriona Goldmann, Alfredo Ferro, Vito Latora, Costantino Pitzalis, Myles J. Lewis
Summary: Gene-gene interaction network analysis of RNA sequencing in early rheumatoid arthritis can provide insights into disease pathogenesis and improve treatment response prediction models.
ARTHRITIS RESEARCH & THERAPY
(2022)