Osteoarthritis (OA) is a degenerative whole joint disease, for which no preventative or therapeutic biological interventions are available. This is likely due to the fact that OA pathogenesis includes several signaling pathways, whose interactions remain unclear, especially at disease onset. Early OA is characterized by three key events: a rarely considered early phase of proliferation of cartilage-resident cells, in contrast to well-established increased synthesis, and degradation of extracellular matrix components and inflammation, associated with OA progression. We focused on the question, which of these key events are regulated by growth factors, inflammatory cytokines, and/or miRNA abundance. Collectively, we elucidated a specific sequence of the OA key events that are described best as a very early phase of proliferation of human articular cartilage (AC) cells and concomitant anabolic/catabolic effects that are accompanied by incipient pro-inflammatory effects. Many of the reviewed factors appeared able to induce one or two key events. Only one factor, fibroblast growth factor 2 (FGF2), is capable of concomitantly inducing all key events. Moreover, AC cell proliferation cannot be induced and, in fact, is suppressed by inflammatory signaling, suggesting that inflammatory signaling cannot be the sole inductor of all early OA key events, especially at disease onset.
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http://dx.doi.org/10.3390/ijms19082282 | DOI Listing |
Aging Clin Exp Res
January 2025
Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
Objective: This study aims to analyze adverse drug events (ADE) related to romosozumab from the second quarter of 2019 to the third quarter of 2023 from FAERS database.
Methods: The ADE data related to romosozumab from 2019 Q2 to 2023 Q3 were collected. After data normalization, four signal strength quantification algorithms were used: ROR (Reporting Odds Ratios), PRR (Proportional Reporting Ratios), BCPNN (Bayesian Confidence Propagation Neural Network), and EBGM (Empirical Bayesian Geometric Mean).
Pediatr Cardiol
January 2025
The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA.
The C3PO collaborative, with a history of successful quality improvement (QI) initiatives, leveraged registry participants to develop a multi-center QI initiative to reduce adverse events (AEs) in congenital cardiac catheterization. A 32-person, interdisciplinary working group analyzed audited data for all congenital cardiac catheterization cases from 2014-2017. The primary outcome was the occurrence of any high-severity (level 3/4/5) AE.
View Article and Find Full Text PDFNano Lett
January 2025
Department of Mechanical Engineering & Materials Science, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.
The development of accurate methods for determining how alloy surfaces spontaneously restructure under reactive and corrosive environments is a key, long-standing, grand challenge in materials science. Using machine learning-accelerated density functional theory and rare-event methods, in conjunction with environmental transmission electron microscopy (ETEM), we examine the interplay between surface reconstructions and preferential segregation tendencies of CuNi(100) surfaces under oxidation conditions. Our modeling approach predicts that oxygen-induced Ni segregation in CuNi alloys favors Cu(100)-O c(2 × 2) reconstruction and destabilizes the Cu(100)-O (2√2 × √2)45° missing row reconstruction (MRR).
View Article and Find Full Text PDFASN Neuro
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
We previously identified a role for dAuxilin (dAux), the fly homolog of Cyclin G-associated kinase, in glial autophagy contributing to Parkinson's disease (PD). To further dissect the mechanism, we present evidence here that lack of glial dAux enhanced the phosphorylation of the autophagy-related protein Atg9 at two newly identified threonine residues, T62 and T69. The enhanced Atg9 phosphorylation in the absence of dAux promotes autophagosome formation and Atg9 trafficking to the autophagosomes in glia.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway.
Objective: Previous studies on the efficacy of methotrexate in people with hand osteoarthritis (OA) have shown conflicting results. The MERINO trial aims to investigate the efficacy and safety of methotrexate in people with painful inflammatory erosive hand OA.
Design: In total 163 participants with erosive hand OA, synovitis by ultrasound, and finger joint pain of 40-80 mm on a visual analogue scale (VAS) will be recruited from a rheumatology outpatient clinic.
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