Betaine Attenuates Osteoarthritis by Inhibiting Osteoclastogenesis and Angiogenesis in Subchondral Bone DOI Creative Commons
Yajun Wang, Jin Cui,

Gu Zhengrong

et al.

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 29, 2021

Osteoarthritis (OA) is the most common type of arthritis with no effective therapy. Subchondral bone and overlying articular cartilage are closely associated function as "osteo-chondral unit" in joint. Abnormal mechanical load leads to activated osteoclast activity increased resorption subchondral bone, which implicated onset OA pathogenesis. Thus, inhibiting activation could prevent onset. Betaine, isolated from Lycii Radicis Cortex (LRC), has been demonstrated exert anti-inflammatory, antifibrotic antiangiogenic properties. Here, we evaluated effects betaine on anterior cruciate ligament transection (ACLT)-induced mice. We observed that decreased number matrix metalloproteinase 13 (MMP-13)-positive collagen X (Col X)-positive cells, prevented proteoglycan loss lowered OARSI score. Betaine thickness calcified expression level lubricin. Moreover, normalized uncoupled remodeling defined by trabecular pattern factor (Tb.pf) plate (SBP). Additionally, aberrant angiogenesis was blunted treatment. Mechanistically, suppressed osteoclastogenesis vitro reactive oxygen species (ROS) production subsequent mitogen-activated protein kinase (MAPK) signaling. These data attenuated progression hyperactivated maintaining microarchitecture bone.

Language: Английский

Chondrocyte membrane–coated nanoparticles promote drug retention and halt cartilage damage in rat and canine osteoarthritis DOI
Ronghui Deng, Ruifang Zhao, Zining Zhang

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(735)

Published: Feb. 21, 2024

Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. A challenge in the development disease-modifying drugs effective delivery to chondrocytes. The unique structure promotes rapid clearance through synovial fluid, and dense avascular cartilage extracellular matrix (ECM) limits drug penetration. Here, we show that poly(lactide- co -glycolic acid) nanoparticles coated chondrocyte membranes (CM-NPs) were preferentially taken up rat chondrocytes ex vivo compared with uncoated nanoparticles. Internalization CM-NPs was mediated primarily E-cadherin, clathrin-mediated endocytosis, micropinocytosis. These adhered ECM knee joints penetrated deeply into residence time more than 34 days. Simulated fluid studies showed loaded Wnt pathway inhibitor, adavivint (CM-NPs-Ada), delayed catabolic metabolism human explants under inflammatory conditions. In surgical model OA, drug-loaded effectively restored gait, attenuated periarticular bone remodeling, provided chondroprotection against degeneration. OA progression also mitigated CM-NPs-Ada canine anterior cruciate ligament transection. results demonstrate feasibility using membrane–coated improve pharmacokinetics efficacy anti-OA drugs.

Language: Английский

Citations

41
Inflammatory Fibroblast‐Like Synoviocyte‐Derived Exosomes Aggravate Osteoarthritis via Enhancing Macrophage Glycolysis DOI Creative Commons
Bin Liu,

Yansi Xian,

Xiang Chen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Feb. 11, 2024

Abstract The severity of osteoarthritis (OA) and cartilage degeneration is highly associated with synovial inflammation. Although recent investigations have revealed a dysregulated crosstalk between fibroblast‐like synoviocytes (FLSs) macrophages in the pathogenesis synovitis, limited knowledge available regarding involvement exosomes. Here, increased exosome secretion observed FLSs from OA patients. Notably, internalization inflammatory FLS‐derived exosomes (inf‐exo) can enhance M1 polarization macrophages, which further induces an OA‐like phenotype co‐cultured chondrocytes. Intra‐articular injection inf‐exo synovitis exacerbates progression murine models. In addition, it demonstrated that stimulation triggers activation glycolysis. Inhibition glycolysis using 2‐DG successfully attenuates excessive triggered by inf‐exo. Mechanistically, HIF1A identified as determinant transcription factor, inhibition which, both pharmacologically or genetically, relieves macrophage inflammation inf‐exo‐induced hyperglycolysis. Furthermore, vivo administration inhibitor alleviates experimental OA. results provide novel insights into pathogenesis, suggesting dysfunction represents attractive target for therapy.

Language: Английский

Citations

40
Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis DOI
Lei Yang, Wenzhao Li, Yuanjin Zhao

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(31), P. 20101 - 20110

Published: July 23, 2024

Osteoarthritis (OA) is a prevalent degenerative disease that afflicts more than 250 million people worldwide, impairing their mobility and quality of life. However, conventional drug therapy palliative. Exosomes (Exo), although with the potential to fundamentally repair cartilage, face challenges in efficient enrichment delivery. In this study, we developed magnetic polysaccharide hydrogel particles as microcarriers for synergistic OA. The were composed modified natural polysaccharides, hyaluronic acid (HAMA), chondroitin sulfate (CSMA), generated from microfluidic electrospray combination cryogelation process. Magnetic nanoparticles spiny structures capable capturing stem cell Exo encapsulated within together an anti-inflammatory diclofenac sodium (DS). released DS had effect alleviating OA symptoms promoting cartilage repair. vitro vivo results demonstrated excellent performance microcarrier treatment. We believe work has other related diseases.

Language: Английский

Citations

23
Opsonization Inveigles Macrophages Engulfing Carrier‐Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy DOI Creative Commons
Huirong Huang,

Shimin Zheng,

Jianing Wu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: April 9, 2024

Abstract Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated an imbalance of M1/M2 macrophages in the synovial cavities contributes to progression, regulating M1 M2 polarization can be potential therapeutic strategy. Basing on inherent immune mechanism pathological environment OA, immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) developed, its evaluated. After intra‐articular administration, IgG conjugation facilitates recognition engulfment nanoparticles macrophages. The internalized disassemble response increased oxidative stress, released bilirubin (BR) JPH203 scavenge reactive oxygen species (ROS), inhibit nuclear factor kappa‐B pathway, suppress activated mammalian target rapamycin result repolarization enhance M2/M1 ratios. Suppression IgG/BRJ promotes protection repair rat model, thereby improving outcomes. This strategy opsonization involving engulf carrier‐free BR/JPH203 therapy holds great intervention treatment.

Language: Английский

Citations

20
Clinical phenotypes, molecular endotypes and theratypes in OA therapeutic development DOI
Ali Mobasheri, Richard F. Loeser

Nature Reviews Rheumatology, Journal Year: 2024, Volume and Issue: 20(9), P. 525 - 526

Published: May 17, 2024

Language: Английский

Citations

17
Osteoarthritis DOI
Su’an Tang, Changqing Zhang, Win Min Oo

et al.

Nature Reviews Disease Primers, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 13, 2025

Language: Английский

Citations

5
A Library of Polyphenol‐Amino Acid Condensates for High‐Throughput Continuous Flow Production of Nanomedicines with Ultra‐High Drug Loading DOI Creative Commons

Zeng Yi,

Xiaomin Ma,

Qiulan Tong

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Synthesizing high drug‐loading nanomedicines remains a formidable challenge, and achieving universally applicable, continuous, large‐scale engineered production of such presents even greater difficulties. This study scalable library polyphenol‐amino acid condensates. By selecting amino acids, the enables precise customization key properties, as carrier capacity, bioactivity, other critical attributes, offering versatile range options for various application scenarios. Leveraging properties solvent‐mediated disassembly reassembly condensates achieved an ultra‐high drug loading 86% paclitaxel. For poorly soluble molecules, capacity exceeded 50%, indicating broad applicability. Furthermore, employing continuous microfluidic device, rate can reach 5 mL min −1 (36 g per day), with nanoparticle size precisely tunable polydispersity index (PDI) below 0.2. The polyphenol‐based demonstrates efficient cellular uptake and, in three distinct animal models, has been shown to enhance therapeutic efficacy paclitaxel without significant side effects. streamlined, efficient, approach using microfluidics produce loading, promising strategy nanoformulation drugs.

Language: Английский

Citations

3
CD34hi subset of synovial fibroblasts contributes to fibrotic phenotype of human knee osteoarthritis DOI Creative Commons
Junya Miyahara, Yasunori Omata,

Ryota Chijimatsu

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(2)

Published: Jan. 22, 2025

Osteoarthritis (OA) shows various clinical manifestations depending on the status of its joint components. We aimed to identify synovial cell subsets responsible for OA pathophysiology by comprehensive analyses human synovium samples in single-cell resolution. Two distinct tissue groups were classified gene expression profiles RNA-Seq: inflammatory and fibrotic. The group exhibited high cytokines, histologically infiltrate, a more severe pain score. fibrotic showed higher fibroblast growth factor (FGFs) bone morphogenetic proteins (BMPs), perivascular fibrosis, lower In RNA-Seq (scRNA-Seq) cells, MERTKloCD206lo macrophages CD34hi fibroblasts associated with groups, respectively. Among 3 subsets, CD34loTHY1lo CD34loTHY1hi influenced immune whereas mural endothelial cells. Particularly, CD34hiCD70hi promoted proliferation Tregs, potentially suppressing synovitis protecting articular cartilage. Elucidation mechanisms underlying regulation these may lead novel strategies therapeutics.

Language: Английский

Citations

2
New Trends in Pharmacological Treatments for Osteoarthritis DOI Creative Commons
Xiaoyan Cai, Shiwen Yuan, Yanting Zeng

et al.

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: April 15, 2021

Osteoarthritis (OA) is the leading cause of function loss and disability among elderly, with significant burden on individual society. It a severe disease for its high rates, morbidity, costs, increased mortality. Multifactorial etiologies contribute to occurrence development OA. The heterogeneous condition poses challenge effective treatment OA; however, emerging treatments are promising bring benefits OA management in future. This narrative review will discuss recent developments agents OA, including potential disease-modifying osteoarthritis drugs (DMOADs) novel therapeutics pain relief. focus more that have been clinical trials, as well attractive applications preclinical research. In past few years, it has realized complex interaction multifactorial mechanisms involved pathophysiology authors believe there no miracle therapeutic strategy fitting all patients. phenotyping would be helpful therapy selection. A variety targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, peripheral nociceptive pathways expected reshape landscape over next years. Precise randomized controlled trials (RCTs) identify safety efficacy therapies specific patients phenotypes.

Language: Английский

Citations

79
Injectable Natural Polymer Hydrogels for Treatment of Knee Osteoarthritis DOI
Xiaojie Lin,

Ching Ting Tsao,

Masayuki Kyomoto

et al.

Advanced Healthcare Materials, Journal Year: 2021, Volume and Issue: 11(9)

Published: Sept. 17, 2021

Abstract Osteoarthritis (OA) is a serious chronic and degenerative disease that increasingly occurs in the aged population. Its current clinical treatments are limited to symptom relief cannot regenerate cartilage. Although better understanding of OA pathophysiology has been facilitating development novel therapeutic regimen, delivery therapeutics target sites with minimal invasiveness, high retention, side effects remains challenge. Biocompatible hydrogels have recognized be highly promising for controlled release biologics tissue repair. In this review, approaches challenges treatment, unique properties injectable natural polymer as system overcome presented. The common methods fabrication polysaccharide‐based their composition on treatment detailed. strategies use loading cargos also covered. Finally, recent efforts highlighted, limitations discussed.

Language: Английский

Citations

71