Article
Biochemistry & Molecular Biology
Manuela Minguzzi, Veronica Panichi, Stefania D'Adamo, Silvia Cetrullo, Luca Cattini, Flavio Flamigni, Erminia Mariani, Rosa Maria Borzi
Summary: Notch signaling pathway plays a critical role in cartilage development and homeostasis, with NOTCH1 being the key receptor that can affect the health status of osteoarthritis chondrocytes by regulating proliferation, hypertrophy, and terminal differentiation. Silencing NOTCH1 showed a healthier phenotype in OA chondrocytes, suggesting it is a convenient therapeutic target to attenuate OA progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Zidong Wang, Bei Wang, Jian Zhang, Zhensong Wu, Liankui Yu, Zhongye Sun
Summary: The blockade of the CCL2/CCR2 axis plays a role in delaying the progression of chondrocyte hypertrophy, involving the regulation of various gene expressions and chondrocyte functions.
MEDICAL SCIENCE MONITOR
(2021)
Article
Biochemistry & Molecular Biology
Bo Young Jeong, Kyung Hwa Cho, Se-Hee Yoon, Chang Gyo Park, Hwan-Woo Park, Hoi Young Lee
Summary: LPA induces DDR2 expression through the activation of the PI3K/Akt/mTOR/HIF-1α/Twist1 signaling axes, aggravating ovarian cancer cell invasion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Li Chen, Xiangyi Kong, Yi Fang, Shishir Paunikar, Xiangyu Wang, James A. L. Brown, Emer Bourke, Xingrui Li, Jing Wang
Summary: Discoidin domain receptor tyrosine kinases (DDRs) are a type of receptor tyrosine kinases associated with various diseases, widely expressed in different cell types and involved in signaling pathways, closely related to the development and progression of solid tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Nathalie G. M. Thielen, Margot Neefjes, Elly L. Vitters, Henk M. van Beuningen, Arjen B. Blom, Marije I. Koenders, Peter L. E. M. van Lent, Fons A. J. van de Loo, Esmeralda N. Blaney Davidson, Arjan P. M. van Caam, Peter M. van der Kraan
Summary: During osteoarthritis, TGF-beta signaling pathways contribute to the hypertrophy-like phenotype in chondrocytes. This study found that ALK5 kinase activity is essential for the induction of crucial hypertrophy factors in TGF-beta-stimulated chondrocytes.
Article
Medicine, General & Internal
Jin-Ju Kim, Judith M. David, Sydney S. Wilbon, Javier Santos, Devang M. Patel, Anis Ahmad, Alla Mitrofanova, Xiaochen Liu, Shamroop K. Mallela, Gloria M. Ducasa, Mengyuan Ge, Alexis J. Sloan, Hassan Al-Ali, Marcia Boulina, Armando J. Mendez, Gabriel N. Contreras, Marco Prunotto, Anjum Sohail, Rafael Fridman, Jeffrey H. Miner, Sandra Merscher, Alessia Fornoni
Summary: DDR1 activation mediated by Col I induces CD36-mediated podocyte lipotoxic injury in Alport Syndrome mice. Ezetimibe interferes with the CD36/DDR1 interaction, thus protecting renal function. Targeting the Col I/DDR1 pathway may represent a new therapeutic strategy for patients with AS and CKD associated with Col4 mutations.
Article
Biology
Kieop Park, Ranjay Jayadev, Sara G. Payne, Isabel W. Kenny-Ganzert, Qiuyi Chi, Daniel S. Costa, William Ramos-Lewis, Siddharthan B. Thendral, David R. Sherwood
Summary: Separate tissues are connected through adjoining basement membranes to fulfill their barrier, exchange, and support functions. The robust and balanced cell adhesion at these connections is essential for withstanding tissue movement. However, the mechanism by which cells achieve synchronized adhesion to connect tissues remains unclear. This study reveals that type IV collagen both fastens the linkage and activates the collagen receptor DDR-2 in the utse and seam tissues, coordinating the strengthening of integrin adhesion through the LET-60/Ras signaling pathway.
Article
Biochemistry & Molecular Biology
Qingyun Liu, Xiaolong Wang, Yazhuo Chen, Xiao Ma, Xiaomin Kang, Fang He, Dongxu Feng, Yan Zhang
Summary: Chronic systemic inflammation causes severe disorders and diseases. Exploring a new target for effective treatment is crucial. This study showed that Ddr2 has a protective role against inflammation in myeloid lineage cells. Mechanistically, Ddr2 promotes macrophage repolarization and is critical in macrophage-mediated inflammation. This research provides a potential target for intervention in inflammation and related diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Kaouther Ben Arfi, Christophe Schneider, Amar Bennasroune, Nicole Bouland, Aurore Wolak-Thierry, Guillaume Collin, Cuong Cao Le, Kevin Toussaint, Cathy Hachet, Veronique Lehrter, Stephane Dedieu, Olivier Bouche, Hamid Morjani, Camille Boulagnon-Rombi, Aline Appert-Collin
Summary: This study found that high expression of DDR1 is associated with worse event-free survival in CRC patients, and it may play a role in the invasive properties of colon adenocarcinoma.
Article
Rheumatology
Hannah Swahn, Kun Li, Tomas Duffy, Merissa Olmer, Darryl D. D'Lima, Tony S. Mondala, Padmaja Natarajan, Steven R. Head, Martin K. Lotz
Summary: This study analyzed the cells of healthy and osteoarthritis knees at the single-cell level using scRNA-seq. The results identified a pathogenic cell cluster in both articular cartilage and meniscus, which is mainly regulated by FAP and ZEB1 and is expanded in osteoarthritis. These findings provide new therapeutic targets for osteoarthritis.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Wenyu Fu, Aubryanna Hettinghouse, Yujianan Chen, Wenhuo Hu, Xiang Ding, Meng Chen, Yuanjing Ding, Jyoti Mundra, Wenhao Song, Ronghan Liu, Young-Su Yi, Mukundan Attur, Jonathan Samuels, Eric Strauss, Philipp Leucht, Ran Schwarzkopf, Chuan-Ju Liu
Summary: This study identifies 14-3-3ε as an inducible component of the TNFR2 receptor complex in chondrocytes in response to PGRN, presenting a previously unrecognized TNFR2 pathway in the pathogenesis of osteoarthritis.
ANNALS OF THE RHEUMATIC DISEASES
(2021)
Article
Rheumatology
Haiyan Zhang, Yan Shao, Zihao Yao, Liangliang Liu, Hongbo Zhang, Jianbin Yin, Haoyu Xie, Kai Li, Pinglin Lai, Hua Zeng, Guozhi Xiao, Chun Zeng, Daozhang Cai, Xiaochun Bai
Summary: This study investigated the role of mechanical stress in cartilage ageing and osteoarthritis (OA) progression. It was found that mechanical overloading accelerated senescence in chondrocytes and articular cartilage. FBXW7 expression was downregulated in primary chondrocytes, mice cartilage, and cartilage of OA patients. FBXW7 deletion in chondrocytes induced chondrocyte senescence and accelerated cartilage catabolism, exacerbating OA. However, intra-articular injection of adenovirus expressing Fbxw7 alleviated OA in mice. Mechanistically, mechanical overloading decreased Fbxw7 mRNA transcription and FBXW7-mediated MKK7 degradation, stimulating JNK signalling. Inhibition of JNK activity improved chondrocyte senescence and cartilage degeneration.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Kai-di Wang, Xiang Ding, Nan Jiang, Chao Zeng, Jing Wu, Xian-yi Cai, Aubryanna Hettinghouse, Asya Khleborodova, Zi-Ning Lei, Zhe-Sheng Chen, Guang-hua Lei, Chuan-ju Liu
Summary: Through screening of FDA-approved drug library, studying the chondroprotective effects of digoxin in vitro, defining the therapeutic effects of digoxin in a surgically-induced OA model, conducting a cohort study to examine the relationship between digoxin use and OA-associated joint replacement risk, identifying digoxin's binding to LRP4, and using various assays including CRISPR-Cas9 genome editing to study the dependence of digoxin regulation on chondrocytes on LRP4.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Immunology
Huangming Zhuang, Bin Li, Ting Xie, Changgeng Xu, Xunshan Ren, Fuze Jiang, Tianrun Lei, Panghu Zhou
Summary: 3-IAld reduces inflammation in osteoarthritis through the AhR-NF-Kappa B signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cell Biology
Anais Defois, Nina Bon, Alexandre Charpentier, Melina Georget, Nicolas Gaigeard, Frederic Blanchard, Antoine Hamel, Denis Waast, Jean Armengaud, Ophelie Renoult, Claire Pecqueur, Yves Maugars, Marie-Astrid Boutet, Jerome Guicheux, Claire Vinatier
Summary: This study reveals a strong association between inflammation and metabolic dysregulation in osteoarthritic chondrocytes. Inflammation affects metabolic-related genes and leads to increased glycolysis and decreased mitochondrial respiration in osteoarthritic chondrocytes. These findings provide important insights for further understanding the mechanisms of osteoarthritis.
CELL COMMUNICATION AND SIGNALING
(2023)