Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2896 - 2896

Опубликована: Март 22, 2025

Links between cathepsin K and the pathophysiology of osteoarthritis (OA) can be established, not least because overabundance in serum OA patients upregulation degraded cartilage animal models OA. Chondrocytes, chondroclasts, or osteoclasts contribute to accumulated at diseased osteochondral junction. After a general presentation physiology, as well its degradation processes, we describe function effect on via type II collagen cleavage. An overview most promising inhibitors is then presented, together with their vitro effects. Although intensive research initially focused bone resorption, there growing interest potential these drugs prevent degradation. In this review, summarize pre-clinical clinical trials that support use treatment To date, no molecules are commercially available, although few have undergone trials, but believe development could broaden therapeutic arsenal for

Язык: Английский

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Engineered mesenchymal stromal cells with interleukin-1beta sticky-trap attenuate osteoarthritis in knee joints

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Апрель 8, 2025

Osteoarthritis (OA) is a common chronic inflammatory joint disease, in which innate immunity plays pivotal role pathogenesis. Anti-interleukin-1(IL-1) therapies have shown inconsistent results clinical trials, potentially due to mismatch the spatial and temporal dynamics of interleukin-1beta (IL-1β) production therapeutic interventions. To address this issue, we developed novel IL-1β "sticky-trap" utilizing cell gene-based technologies from our lab evaluated its efficacy reducing osteoarthritis progression using murine destabilization medial meniscus (DMM) OA model compact bone-derived mesenchymal stromal (MSC)-based gene expression system. The extracellular domain interleukin-1 receptor 2 (IL1R2) was employed design sticky IL1R2 trap (stkIL1R2). A MSC line engineered for delivery. Although stkIL1R2 undetectable supernatants by enzyme-linked immunosorbent assay (ELISA) Western blot, it localized on surface matrix (ECM) demonstrated specific binding fluorescent protein-fused assay. Doxycycline (Dox)-induced significantly inhibited lipocalin-2 (LCN2) biomarker activity. For vivo experiments, 5 × 104 Dox-inducible stkIL1R2f expressing MSCs were injected into knee joints DMM mice. Bioluminescence imaging revealed survival up 7 weeks post-injection. Histological analyses at 10 post-injection, including Safranin-O Masson trichrome staining, showed that treated exhibited less cartilage degradation synovitis compared controls, as assessed Research Society International (OARSI) scoring femur, tibia, synovium. Moreover, treatment reduced metalloproteinases-13 (MMP-13) positive cells collagen type II affected joints. In conclusion, an inducible IL1 sticky-trap, ECM specifically bound IL-1β. These survived normal delayed inflammation model. This study introduces promising approach combat progression.

Язык: Английский

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Bibliometric analysis of research trends and emerging insights of osteoarthritis and chondrocyte hypertrophy

Frontiers in Surgery, Год журнала: 2025, Номер 12

Опубликована: Апрель 10, 2025

This study aims to systematically analyze the intersection of OA and chondrocyte hypertrophy using bibliometric methods, providing an quantitative comprehensive overview current research status emerging trends in this field. Relevant publications were retrieved from Web Science Core Collection database search query TS = ("chondrocyte* hypertroph*" OR "hypertrophic chondrocyte*" "cartilage hypertroph*") AND ("osteoarthriti*" "OA" "degenerative arthritis"). Several tools, including Vosviewer, CiteSpace, R package (bibliometrix), Excel 2021, utilized on OA. A total 639 publications, published between 1995 2025, identified. The findings indicate a steady global increase hypertrophy, with increasing number studies being high-impact journals, suggesting promising developmental trajectory. China United States are leading OSTEOARTHRITIS CARTILAGE is identified as core journal area, while ANNALS OF THE RHEUMATIC DISEASES has highest impact factor among top publishing journals. Keyword analysis reveals that hotspots primarily focus stem cells, tissue engineering, cartilage repair, inflammation, oxidative stress, autophagy, apoptosis, senescence, related bioactive factors. elucidates at crucial references for future research. Future should continue these potential therapeutic approaches, key phenotypes, regulatory mechanisms, enhance international cooperation develop more effective strategies treatments

Язык: Английский

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Therapeutic potential of CHI3L1 in osteoarthritis: Inhibition of cartilage matrix degradation and inflammation through TLR4-MAPK-STAT1 pathway

International Immunopharmacology, Год журнала: 2025, Номер 156, С. 114684 - 114684

Опубликована: Апрель 19, 2025

CHI3L1 has been identified as a protein expressed in various tissues and tumor tissues, playing critical roles diverse physiological pathological processes such inflammation, oxidative stress, cell death, immune regulation. Previous studies have indicated that the elevated levels synovial fluid serum of osteoarthritis patients may serve biomarker for osteoarthritis. However, mechanisms by which affects chondrocytes significance its upregulated expression remain to be fully elucidated. This study aims investigate effects on elucidate molecular mechanisms. Interleukin-1 beta (IL-1β) was utilized vitro induce an inflammatory injury model chondrocytes. The destabilization medial meniscus (DMM) surgery employed establish mouse vivo. Experimental techniques, including Western blot, RT-qPCR, immunofluorescence, transcriptome sequencing, co-immunoprecipitation, were applied Microcomputed tomography (micro-CT), X-ray imaging, IHC used evaluate impact knee joint mice. In experiments demonstrated enhanced matrix synthesis markers, suppressed degradation indicators, reduced factors vivo showed intra-articular overexpression via rAAV-Chi3l1 alleviated cartilage degeneration inflammation murine model. Mechanistically, integrated transcriptomic profiling functional assays revealed interacts with TLR4 attenuate MAPK phosphorylation, thereby inhibiting STAT1 phosphorylation nuclear translocation. is alleviates through TLR4-MAPK-STAT1 pathway, progression These findings indicate cytokine protective represent promising therapeutic target alleviating objective this further underlying exerts influence study, it proposed maintains homeostasis activation signaling pathway. We established role maintaining homeostasis, potential receptors pathways associated CHI3L1, elucidated action. osteoarthritic tissue not yet investigated. Further research needed secreted

Язык: Английский

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Therapeutic application of regulatory T cell in osteoarthritis

Journal of Microbiology Immunology and Infection, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Regulatory T cells (Tregs) are the specific cell population that suppress inflammatory immunity. Independent of their inhibitory activities, Tregs exhibit unique capacity to repair tissue damage. Rapid progresses made in processing and engineering for clinical applications. have been used treatment autoimmune diseases, transplantation rejection graft-versus-host disease. Osteoarthritis is one major diseases affect at least 600 million people worldwide. characterized by physical erosion cartilage, accompanied with chronic low-grade inflammation. possess abilities increase osteoclast differentiation bone resorption, damage, mass. therefore candidate therapeutics osteoarthritis both inflammation resolution repairing. In this review, we will summarize recent development using immunotherapy, potential osteoarthritis.

Язык: Английский

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RNA-binding protein HuR interacts with UFM1 mRNA to ameliorate chondrocyte inflammation, apoptosis and extracellular matrix degradation

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 28, 2025

Язык: Английский

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Are Osteoarthritis Inflammation and Its Related Sensorimotor Interactions Both Noteworthy and Modifiable Key Players?

Опубликована: Май 22, 2025

Joints are sensitive structures whose qualitative and quantitative components depend not only on the harmonious interactions of hormones, enzymes, vitamins, minerals protein, but also stresses put upon them by function as well their intrinsic extrinsic neuromotor environments, activity integrity. This paper reviews some recent pathological insights regarding synovial joint’s lining its immune cellular responses that indicate when traumatized may evoke a possible unstoppable cascade inflammation cartilage destruction unless abated in timely way. One essential movement correlate especially fail to limit spread osteoarthritis oftentimes severe repercussions, namely muscle dysfunction is specifically discussed. Based what known we argue favor untapped utility efforts reverse or mitigate post traumatic arthritis, face persistent mechanical impacts.

Язык: Английский

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Exosomal miR-574-3p from adipose-derived mesenchymal stem modulates CRIM1/BMPs signaling to restrain chondrocytes hypertrophy and inflammatory response in knee osteoarthritis

International Immunopharmacology, Год журнала: 2025, Номер 159, С. 114916 - 114916

Опубликована: Май 27, 2025

Язык: Английский

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Association of organs-crosstalk with the pathogenesis of osteoarthritis: cartilage as a key player

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Июнь 5, 2025

Degeneration of articular cartilage is the hallmark pathologic change in osteoarthritis (OA). Cartilage not only serves as a shock-absorbing structure for movement but also regulated by organs other than bone, while chondrocytes secrete cytokines that influence these organs. The concept organ axis refers to regulatory pathways formed between via cytokine signaling. communication network established and constitutes cartilage-organ axis. Through this axis, regulate chondrocyte proliferation apoptosis. It evident play central role connecting various progression OA, prompting interest strategies intervene damage modulating This review presents, first time, system summarizing effects extraosseous on through factors alter OA progression. aim fully elucidate different cartilage, thus providing insights into treatment systemic diseases.

Язык: Английский

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Relationship between systemic immune-inflammation index and osteoarthritis: a cross-sectional study from the NHANES 2005–2018

Frontiers in Medicine, Год журнала: 2024, Номер 11

Опубликована: Авг. 14, 2024

Objective The study aimed to explore the relationship between systemic inflammatory response index (SIRI) levels and osteoarthritis (OA) using cross-sectional data from National Health Nutrition Examination Survey (NHANES) database 2005 2018. Methods Using NHANES 2018, we included 11,381 participants divided into OA ( n = 1,437) non-OA 9,944) groups. Weighted multivariable regression models subgroup analyses were employed investigate SIRI OA. Additionally, restricted cubic spline used nonlinear relationships. Results This enrolled aged ≥20 years, including 1,437 (14%) with analysis in fully adjusted Model 3 indicated a correlation higher of (log 2 -transformed) an increased risk (odds ratio: 1.150; 95% confidence interval: 1.000–1.323, p < 0.05). Interaction tests showed that variables did not significantly affect this for interaction all >0.05). model revealed log risk, threshold effect showing 4.757 as critical value SIRI. <4.757 almost unchanged whereas >4.757 rapidly increasing risk. Conclusion positive 4.757, holds clinical practical applications. our indicates is novel, clinically valuable, convenient biomarker can be predict adults.

Язык: Английский

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