Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Aging Cell, Год журнала: 2024, Номер 23(4)

Опубликована: Янв. 29, 2024

Abstract Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to pain, disability, diminished quality of life. Although considerable research has been conducted, precise molecular mechanisms propelling OA pathogenesis continue be elusive, thereby impeding development effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in early stage OA. This marked by escalated osteoclast‐mediated resorption, subsequent imbalances metabolism, accelerated turnover, decrease volume, contributing significantly pathological changes. While role hallmarks extensively elucidated from perspective chondrocytes, their connection with osteoclasts not yet fully understood. There compelling evidence suggest that age‐related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, mitochondrial dysfunction, can stimulate osteoclast activity. review intends systematically discuss how contribute pathogenesis, placing particular emphasis on age‐induced shifts It also aims future probing into therapeutic approaches targeting during aging.

Язык: Английский

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Smart responsive in situ hydrogel systems applied in bone tissue engineering

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Май 28, 2024

The repair of irregular bone tissue suffers severe clinical problems due to the scarcity an appropriate therapeutic carrier that can match dynamic and complex damage. Fortunately, stimuli-responsive in situ hydrogel systems are triggered by a special microenvironment could be ideal method regenerating because injectability, gelatin, spatiotemporally tunable drug release. Herein, we introduce two main stimulus-response approaches, exogenous endogenous, forming hydrogels engineering. First, summarize specific distinct responses extensive range external stimuli (e.g., ultraviolet, near-infrared, ultrasound, etc.) form created from biocompatible materials modified various functional groups or hybrid nanoparticles. Furthermore, “smart” hydrogels, which respond endogenous physiological environmental temperature, pH, enzyme, etc.), achieve gelation one injection vivo without additional intervention. Moreover, mild chemistry response-mediated also offer fascinating prospects engineering, such as Diels–Alder, Michael addition, thiol-Michael Schiff reactions, etc. recent developments challenges smart their application administration engineering discussed this review. It is anticipated advanced strategies innovative ideas will exploited field increase quality life for patients with

Язык: Английский

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Regulation of osteoclast-mediated bone resorption by lipids

Bone, Год журнала: 2025, Номер 193, С. 117423 - 117423

Опубликована: Фев. 9, 2025

Язык: Английский

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Jianpi Qingre Tongluo prescription alleviates the senescence-associated secretory phenotype with osteoarthritis by regulating STAG1/TP53/P21 signaling pathway

Journal of Ethnopharmacology, Год журнала: 2024, Номер unknown, С. 118953 - 118953

Опубликована: Окт. 1, 2024

Язык: Английский

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Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head

Molecular Medicine, Год журнала: 2024, Номер 30(1)

Опубликована: Июль 31, 2024

Abstract Background Osteoclast hyperactivation due to the pathological overproduction of reactive oxygen species (ROS) stimulated by glucocorticoids (GCs) is one key drivers behind glucocorticoid-induced osteonecrosis femoral head (GIONFH). The insulin degrading enzyme (IDE), a conserved Zn 2+ metallo-endopeptidase, facilitates DNA binding glucocorticoid receptor and plays substantial role in steroid hormone-related signaling pathways. However, potential IDE pathogenesis GIONFH yet undefined. Methods In this study, we employed network pharmacology bioinformatics analysis explore impact inhibition on with 6bK as an inhibitory agent. Further evidence was collected through vitro osteoclastogenesis experiments vivo evaluations involving methylprednisolone (MPS)-induced mouse model. Results Enrichment indicated redox regulation amid development. findings revealed that could attenuate GCs-stimulated overactivation osteoclast differentiation interfering transcription expression osteoclastic genes (Traf6, Nfatc1, Ctsk). use H 2 DCFDA probe subsequent WB assays introduced effects osteoclastogenesis, linked activation nuclear factor erythroid-derived 2-like (Nrf2)-mediated antioxidant system. Furthermore, Micro-CT scans validated alleviate MPS-induced models. Conclusions Our suggest suppresses hyperactivity GCs-rich environment. This achieved reducing accumulation intracellular ROS via promoting Nrf2-mediated system, thus implying be promising therapeutic target for GIONFH.

Язык: Английский

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The Multifaceted Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 in Osteoarthritis: Regulation of Oxidative Stress and Inflammation

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 6619 - 6633

Опубликована: Сен. 1, 2024

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of cartilage, subchondral bone sclerosis, synovitis, and structural changes in joint. Recent research has highlighted role various genes pathogenesis progression OA, with nuclear factor erythroid 2-related 2 (NRF2) emerging as critical player. NRF2, vital transcription factor, plays key regulating OA microenvironment slowing disease's progression. It modulates expression several antioxidant enzymes, such Heme oxygenase-1 (HO-1) NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, pain, breakdown cartilage extracellular matrix, while also mitigating cell aging death. This review discusses NRF2's impact on stress, aging, death modes (such apoptosis, necroptosis, ferroptosis) OA-affected chondrocytes. The macrophages, synovial fibroblasts was discussed. covers preserving matrix alleviating pain. purpose this to provide comprehensive understanding protective mechanisms highlighting its potential therapeutic target underscoring significance development novel treatment strategies for OA.

Язык: Английский

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NLRP3 Inflammasome-Mediated Osteoarthritis: The Role of Epigenetics

Biology, Год журнала: 2025, Номер 14(1), С. 71 - 71

Опубликована: Янв. 14, 2025

The prevalence of osteoarthritis (OA) notably surges with age and weight gain. most common clinical therapeutic drugs are painkillers, yet they cannot impede the deteriorating course OA. Thus, understanding OA's pathogenesis devising effective therapies is crucial. It generally recognized that inflammation, pyroptosis, OA progression tightly linked. activation NLRP3 inflammasome can lead to discharge pro-inflammatory cytokines Interleukin-1β IL-18, intensifying subsequent inflammatory reactions promoting development. Conversely, imbalance caused by deacetylase-regulated underlies chronic mild inflammation related degenerative diseases. Therefore, this article expounds on mechanism role histone deacetylases (HDACs) in inflammasome-triggered OA, illustrates application HDAC inhibitors striving provide more insights into novel treatment approaches.

Язык: Английский

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Akt2 inhibition alleviates temporomandibular joint osteoarthritis by preventing subchondral bone loss

Arthritis Research & Therapy, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 27, 2025

This study aimed to investigate the role and mechanism of Akt2 pathway in different stages anterior disc displacement (ADD)-induced temporomandibular joint osteoarthritis (TMJOA). A rat model for TMJOA that simulates was established. For inhibit expression subchondral bone, rats were intravenously injected with adeno-associated virus carrying shRNA at a titer 1 × 1012 transducing units/mL 10 days before ADD or sham operations. The euthanized evaluated 8 weeks after surgery, as these time points represented early advanced stage ADD. Immunostaining performed examine location phosphorylated Microcomputed tomography, hematoxylin eosin staining, toluidine blue Western blotting, immunohistochemical immunofluorescence staining used elucidate pathological changes potential mechanisms underlying ADD-induced TMJOA. In TMJOA, rapid condylar bone loss occurred increased phosphorylation macrophages within week post-surgery. At abnormal remodeling degenerative cartilage observed. Inhibiting reduced resorption following surgery while improving morphology Additionally, inhibition alleviated degeneration characterized by decreased number apoptotic chondrocytes, matrix metalloproteinases, collagen type II tissue. is activated mainly during plays an important regulating remodeling. Inhibition could serve prophylactic treatment slow progression

Язык: Английский

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Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis

Arthritis Research & Therapy, Год журнала: 2025, Номер 27(1)

Опубликована: Март 8, 2025

Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, potential effects concerning rheumatoid arthritis (RA) remain underexplored. This study was designed to elucidate associations between Quercetagetin RA, establishing therapeutic of related mechanisms RA treatment. Network pharmacology conducted decipher targets signaling pathways RA. In vitro assays were then explore on osteoclast cell behaviors corresponding pathways. vivo further validated effect collagen antibody-induced (CAIA) mice. The network pharmacological analysis indicated an intimate correlation with RA-related inflammatory osteolysis Pertaining biological validations, 2 µM successfully inhibited LPS-driven differentiation function. qPCR assay Western blot analyses denoted parallel changes osteoclastic marker genes proteins. Further mechanism uncovered stimulating Nrf2/Keap1 pathway moderating Pten/AKT/Nfatc1 axis osteoclasts. revealed 40 mg/kg every day could significantly relief joint destruction CAIA Our presents 's treating outlining suppressing LPS-induced activity, alleviating bone model, thereby laying groundwork translational research eriocauli

Язык: Английский

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Exploring the Therapeutic Potential of MIR‐140‐3p in Osteoarthritis: Targeting CILP and Ferroptosis for Novel Treatment Strategies

Cell Proliferation, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects millions of individuals worldwide, severely impairing mobility, independence, quality life. Emerging evidence suggests ferroptosis critical factor in OA pathogenesis. However, its precise involvement underlying mechanisms remain poorly understood. In this study, we first identified cartilage intermediate layer protein (CILP) mediates the regulation ferroptosis-related genes through hdWGCNA analysis combined with single-cell RNA sequencing. Further investigation revealed significant upregulation CILP expression C28/I2 cells under LPS induction. Mechanistically, bioinformatics differentially expressed miRNAs; qRT-PCR dual-luciferase experiment miR-140-3p was downregulated directly targets CILP. Experimental data further demonstrated regulates ferroptosis, inflammation, oxidative stress by targeting These findings offer valuable insights into molecular miR-140-3p/CILP axis regulating stress, thus providing foundation for developing therapeutic strategies OA.

Язык: Английский

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