Review
Cell Biology
Chenhui Cai, Wenhui Hu, Tongwei Chu
Summary: This review summarizes the findings and observations in the field of iron overload-related osteoarthritis (OA), discussing the cellular and molecular mechanisms associated with iron overload and its negative impact on joint homeostasis. It also highlights the potential value of interrupting the pathological effects of iron overload for the development of improved therapeutics in the field of OA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Thomas A. Nicholson, Michael Sagmeister, Susanne N. Wijesinghe, Hussein Farah, Rowan S. Hardy, Simon W. Jones
Summary: Age-related musculoskeletal disorders, such as sarcopenia, osteoporosis, and arthritis, are common chronic conditions worldwide. Developing safer and more effective pharmacological treatments for these disorders is a clinical necessity. This review explores the potential of oligonucleotide therapies in modifying pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system to address the unmet clinical need. It also discusses the challenges and current approaches in the clinical development of oligonucleotide therapies for musculoskeletal disorders.
Review
Cell Biology
Shefali Mehta, Swapnil Hingole, Varun Chaudhary
Summary: Wnt proteins are lipid-modified secreted proteins that activate multiple signaling pathways, regulating crucial processes during development. Despite being hydrophobic, they can travel several cell distances in the extracellular space. Research has identified factors and mechanisms regulating their expression, secretion, and extracellular travel, recognizing the importance of Wnt protein gradients in maintaining tissue homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Ze Du, Xuanhe You, Diwei Wu, Shishu Huang, Zongke Zhou
Summary: Osteoarthritis (OA) is a leading cause of disabilities in older people, and multiple disease-related molecular networks have been identified. Recent research suggests that rhythmic disturbances in the central nervous system and local joint tissues affect joint homeostasis and exacerbate OA progression. However, the mechanisms of rhythm changes in joint tissues remain poorly understood, and studying the impact of rhythmic genes on metabolism and inflammation could enhance our understanding of OA pathology.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Immunology
Gundula Roesch, Dominique Muschter, Shahed Taheri, Karima El Bagdadi, Christoph Dorn, Andrea Meurer, Frank Zaucke, Arndt F. Schilling, Susanne Graessel, Rainer H. Straub, Zsuzsa Jenei-Lanzl
Summary: Recent studies have shown that beta 2-adrenoceptors (ARs) contribute to the development of osteoarthritis (OA). In this study, the role of beta 2-AR in knee OA was investigated using beta 2-AR-deficient mice. The results showed that beta 2-AR deficiency led to changes in cartilage degeneration, synovial inflammation, and subchondral bone remodeling in OA. These findings suggest that beta 2-AR plays a significant role in OA-related subchondral bone remodeling and could be a potential target for new therapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Orthopedics
G. Roesch, K. El Bagdadi, D. Muschter, S. Taheri, C. Dorn, A. Meurer, R. H. Straub, F. Zaucke, A. F. Schilling, S. Graessel, Z. Jenei-Lanzl
Summary: The study showed that peripheral dampening of sympathetic nervous system activity aggravated osteoarthritis-specific cartilage calcification and subchondral bone thickening, but did not influence cartilage degradation and synovitis.
OSTEOARTHRITIS AND CARTILAGE
(2022)
Review
Cell Biology
Zihao Li, Ziyu Huang, Lunhao Bai
Summary: Osteoarthritis is a common chronic disease that affects cartilage and entire joint tissues. Understanding the complex crosstalk among different joint tissues is critical in elucidating the pathogenic mechanism of OA. This review provides a comprehensive summary of key cells involved in OA pathogenesis and discusses their communication mechanisms and therapeutic potential.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Polymer Science
Elena Iulia Oprita, Andreea Iosageanu, Oana Craciunescu
Summary: This paper reviews the complex structure of osteochondral tissue, the importance of icariin in osteochondral regeneration, and the recent development of hydrogels and scaffolds enriched with icariin. Icariin has chondrogenic and osteogenic effects, making it a promising alternative to growth factors. The use of icariin as a therapeutic approach in regenerative medicine is low-cost and has potential.
Article
Biophysics
Milad Rohanifar, Benjamin B. Johnston, Alexandra L. Davis, Young Guang, Kayla Nommensen, James A. J. Fitzpatrick, Christine N. Pham, Lori A. Setton
Summary: The material properties of synovium, including compressive properties and hydraulic permeability, were measured in this study. These properties can be used to predict drug transport in synovium and improve understanding of drug transport in healthy and pathological joints.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Francesca Manuela Johnson de Sousa Brito, Andrew Butcher, Addolorata Pisconti, Blandine Poulet, Amanda Prior, Gemma Charlesworth, Catherine Sperinck, Michele Scotto di Mase, Ke Liu, George Bou-Gharios, Robert Jurgen van 't Hof, Anna Daroszewska
Summary: Syndecan-3 promotes new bone formation in osteoblasts by enhancing WNT signaling, and its deficiency in mice results in an early osteoporosis-like phenotype due to delayed osteoblast maturation and impaired function. Overexpressing Sdc3 in osteoblasts rescues the low bone volume phenotype and increases bone mass, making SDC3 a potential target for novel bone anabolic drug development.
Review
Genetics & Heredity
Zhuang Li, Jun Lu
Summary: Osteoarthritis (OA) is a common joint disease with irreversible progression. CircRNAs play a vital role in various aspects of OA, including extracellular matrix metabolism, autophagy, apoptosis, chondrocyte proliferation, inflammation, oxidative stress, cartilage development, and chondrogenic differentiation. Although circRNAs have regulatory roles in OA and potential clinical value, further studies are needed.
FRONTIERS IN GENETICS
(2023)
Review
Cell Biology
Chunzhu Song, Kendal Broadie
Summary: Drosophila models of neurological disease, particularly the FXS model, have greatly contributed to our understanding of the pathogenic mechanisms and neurological phenotypes of fragile X syndrome, and have provided potential therapeutic targets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yining Zhang, Yixin Zhao, Zhengsong Xie, Molin Li, Yujiao Liu, Xiaolin Tu
Summary: Our study confirmed that BMP-7 mediates the anabolic actions of Wnt/β-catenin signaling in osteocytes. This provides new evidence for the clinical application of BMP-7-overexpressed osteocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Stefano Coaccioli, Piercarlo Sarzi-Puttini, Panagiotis Zis, Giuseppe Rinonapoli, Giustino Varrassi
Summary: In recent years, there have been interesting advancements in the understanding of the basis of osteoarthritis (OA). Research suggests that cartilage degeneration is preceded by subchondral bone lesions, indicating a key role of this mechanism in the pathogenesis and progression of OA. Chronic low-grade inflammation of the synovial lining, along with immunological and metabolic factors, is now considered crucial in driving inflammation and tissue destruction in OA. Additionally, the role of neuroinflammation and central sensitization mechanisms as underlying causes of chronic pain has been characterized.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Fang Li, Qizhao Tan, Feng Li, Ke Zhang, Zhongjun Liu, Yun Tian, Tengjiao Zhu
Summary: This study reveals that hypoxia in subchondral bone plays a crucial role in the crosstalk between chondrocytes and osteoblasts, and promotes the shift of chondrocytes toward an OA-like phenotype probably by activating the Wnt/beta-catenin signaling pathway in osteoblasts.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Meeting Abstract
Rheumatology
M. Van Mechelen, S. Hayer, K. Van Laere, R. Lories, B. Neerinckx
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Kevin L. Winthrop, John D. Isaacs, Philip J. Mease, Dimitrios T. Boumpas, Xenofon Baraliakos, Jacques-Eric Gottenberg, Stefan Siebert, Marta Mosca, Neil Basu, Dana Orange, R. Lories, Daniel Aletaha, Iain B. McInnes, Tom W. J. Huizinga, Reinhard E. Voll, Ellen M. Gravallese, Ferry C. Breedveld, Josef S. Smolen
Summary: This article summarizes the unmet clinical and scientific needs in the field of rheumatology. It highlights the importance of clinical trial design innovation and the need to better understand the natural history of rheumatic diseases. The article also identifies the specific unmet needs in different rheumatological disease-specific groups and emphasizes the importance of developing therapies and therapeutic strategies for treatment-refractory disease.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Orthopedics
S. A. Elahi, R. Castro-Vinuelas, P. Tanska, R. K. Korhonen, R. Lories, N. Famaey, I. Jonkers
Summary: In silico approach was used to study the main mechanisms of cartilage degeneration in osteoarthritis. Collagen degradation drives degenerative changes in intact and degenerated cartilage, while mechanical loading initially causes proteoglycans depletion in the presence of a focal cartilage defect.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Orthopedics
J. Quintiens, A. De Roover, F. M. F. Cornelis, A. Escribano-Nun, A. Sermon, S. Pazmino, S. Monteagudo, R. J. Lories
Summary: This study identified the hypoxia and Wnt signaling pathways as regulators of ANP32A expression. Hypoxia increased ANP32A levels, while Wnt hyper-activation decreased ANP32A levels. The modulation of the ATM gene by hypoxia and Wnt was also observed. Maintaining hypoxia and limiting Wnt activation are important for protecting against osteoarthritis.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Review
Rheumatology
Jonas J. W. Kuiper, Joerg C. Prinz, Efstratios Stratikos, Piotr Kusnierczyk, Akiko Arakawa, Sebastian Springer, Dillon Mintoff, Ivan Padjen, Russka Shumnalieva, Secil Vural, Ina Koetter, Marleen G. van de Sande, Ayse Boyvat, Joke H. de Boer, George Bertsias, Niek de Vries, Charlotte L. M. Krieckaert, Ines Leal, Natasa Vidovic Valentincic, Ilknur Tugal-Tutkun, Hanane el Khaldi Ahanach, Felicie Costantino, Simon Glatigny, Danijela Mrazovac Zimak, Fabian Loetscher, Floor G. Kerstens, Marija Bakula, Elsa Viera Sousa, Peter Boehm, Kees Bosman, Tony J. Kenna, Simon J. Powis, Maxime Breban, Ahmet Gul, John Bowes, Rik J. U. Lories, Johannes Nowatzky, Gerrit Jan Wolbink, Dennis G. McGonagle, Franktien Turkstra
Summary: The 'MHC-I-opathy' concept describes a group of inflammatory diseases with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. However, the understanding and treatment of these disorders is limited due to patient heterogeneity and lack of systematic investigation. Therefore, interdisciplinary collaboration is needed to decipher the underlying disease mechanisms.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Reem Assi, Chahrazad Cherifi, Frederique M. F. Cornelis, Qiongfei Zhou, Lies Storms, Sofia Pazmino, Rodrigo Coutinho de Almeida, Ingrid Meulenbelt, Rik J. J. Lories, Silvia Monteagudo
Summary: The methylation of H3K79me is reduced in osteoarthritis. Histone demethylase families, such as Jumonji-C and KDM2/7, can increase the levels of H3K79me and targeting KDM2/7 can protect joints against osteoarthritis.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Pharmacology & Pharmacy
Reem Assi, Jolien Quintiens, Silvia Monteagudo, Rik J. J. Lories
Summary: Osteoarthritis is a chronic joint disease characterized by progressive damage to the joints, causing pain and loss of function. Intra-articular drug therapy has emerged as a potential treatment option, with drugs being injected directly into affected joints to optimize drug bioavailability and reduce systemic toxicity. This review explores the current landscape of intra-articular drug therapies for osteoarthritis, including established approaches and those in clinical development. Despite challenges in defining outcome measures and optimizing clinical trial set-ups, advancements in drug development and clinical trial design hold promise for successful therapies for this important disease.
Article
Orthopedics
Stijn Arnaert, Paul Byttebier, Sam Van Rossom, Evie Vereecke, Ilse Jonkers, Edwin Oei, Sita M. A. Bierma-Zeinstra, Rik Lories, Marienke van Middelkoop, Stefan Clockaerts
Summary: This study investigates the characteristics of the anterior tibiotalar fat pad (ATFP) in the ankle joint after one year of an ankle sprain and its correlation with systemic factors and local articular pathology. The results suggest that age, body mass index (BMI), and sex are significantly associated with the T1 intensity of ATFP. Age, diffuse cartilage loss in the lateral talus, and Kellgren and Lawrence score in the tibiotalar joint are negatively associated with the area of ATFP. BMI is positively associated with the ATFP area.
Article
Rheumatology
Manouk de Hooge, Alla Ishchenko, Ann-Sophie De Craemer, Serge Steinfeld, Adrien Nzeusseu, Dirk Elewaut, Rik Lories, Kurt de Vlam, Filip van den Bosch
Summary: This study aimed to examine radiographic axial damage of the sacroiliac joints and spine in patients with psoriatic arthritis (PsA) and spondyloarthritis (SpA) in private and academic Belgian practices. The data comparison between the two patient groups found that patients with SpA tend to have more severe spinal damage compared to those with PsA. In patients with PsA, the cervical spine is more often affected, while in patients with SpA, the location of syndesmophytes is more evenly distributed.
Article
Rheumatology
Manouk de Hooge, Alla Ischenko, Serge Steinfeld, Adrien Nzeusseu, Dirk Elewaut, Rik Lories, Filip van den Bosch, Kurt De Vlam
Summary: This study investigates the association between different definitions of axial involvement and syndesmophytes development in patients with Psoriatic Arthritis (PsA). The results show that the probability of developing syndesmophytes is much higher when axial involvement is determined radiographically rather than clinically, particularly in the context of high CRP.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Mariia Dzhus, Lisa Ehlers, Marjon Wouters, Katrien Jansen, Rik Schrijvers, Lien De Somer, Steven Vanderschueren, Marco Baggio, Leen Moens, Benjamin Verhaaren, Rik Lories, Giorgia Bucciol, Isabelle Meyts
Summary: Deficiency of human adenosine deaminase type 2 (DADA2) is a rare autoimmune disorder characterized by vasculopathy, immune dysregulation, and hematologic abnormalities. Neurological manifestations, particularly strokes, are a significant feature of DADA2, with brain stem and deep gray matter being commonly affected. Other neurological involvements include neuropathies, focal deficits, ophthalmological findings, convulsions, and headaches. Recognizing the diverse neurological manifestations of DADA2 is crucial for accurate diagnosis and appropriate management.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Review
Rheumatology
Ennio Lubrano, Silvia Scriffignano, Kurt de Vlam, Mario Ronga, Fabio Massimo Perrotta, Rik Lories
Summary: Psoriatic arthritis (PsA) is a complex and chronic inflammatory disease that combines arthritis and psoriasis with other conditions and comorbidities. Non-pharmacological approaches such as diet modifications, improved sleep quality, and physical activity have been shown to improve the quality of life for PsA patients.
Article
Cell & Tissue Engineering
Jeremie Zappia, Qiao Tong, Renee Van der Cruyssen, Frederique M. F. Cornelis, Cecile Lambert, Tiago Pinto Coelho, Juliane Grisart, Erika Kague, Rik J. Lories, Marc Muller, Dirk Elewaut, Chrissy L. Hammond, Christelle Sanchez, Yves Henrotin
Summary: Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis. Osteomodulin (OMD), a proteoglycan, is associated with the sclerotic phenotype. This study found that OMD binds to RANKL and inhibits osteoclastogenesis, thus regulating bone remodeling and contributing to bone and cartilage homeostasis. Targeting OMD may be a promising personalized approach for osteoarthritis.
Meeting Abstract
Cell & Tissue Engineering
Rik Lories
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Orthopedics
Q. Zhou, F. Cornelis, S. Monteagudo, R. J. Lories
OSTEOARTHRITIS AND CARTILAGE
(2022)
