Potential Methods of Targeting Cellular Aging Hallmarks to Reverse Osteoarthritic Phenotype of Chondrocytes

He, Yuchen; Lipa, Katelyn E.; Alexander, Peter G.; Clark, Karen; Lin, Hang

doi:10.3390/biology11070996

Cited by 5 publications

(2 citation statements)

References 275 publications

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“…Chronic inflammation has been implicated in both OA development and the aging process. Potentially, targeting cellular aging has become a strategy to reverse the phenotype of OA chondrocytes ( 129 ). Chondrocyte senescence can be regulated by IL-1β.…”

Section: Natural Flavonoids Exhibit Protective Activity Against Oa De...mentioning

confidence: 99%

The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway

Zhou

2023

Front. Endocrinol.

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Osteoarthritis (OA) is a typical joint disease associated with chronic inflammation. The nuclear factor-kappaB (NF-κB) pathway plays an important role in inflammatory activity and inhibiting NF-κB-mediated inflammation can be a potential strategy for treating OA. Flavonoids are a class of naturally occurring polyphenols with anti-inflammatory properties. Structurally, natural flavonoids can be divided into several sub-groups, including flavonols, flavones, flavanols/catechins, flavanones, anthocyanins, and isoflavones. Increasing evidence demonstrates that natural flavonoids exhibit protective activity against the pathological changes of OA by inhibiting the NF-κB signaling pathway. Potentially, natural flavonoids may suppress NF-κB signaling-mediated inflammatory responses, ECM degradation, and chondrocyte apoptosis. The different biological actions of natural flavonoids against the NF-κB signaling pathway in OA chondrocytes might be associated with the differentially substituted groups on the structures. In this review, the efficacy and action mechanism of natural flavonoids against the development of OA are discussed by targeting the NF-κB signaling pathway. Potentially, flavonoids could become useful inhibitors of the NF-κB signaling pathway for the therapeutic management of OA.

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Section: Natural Flavonoids Exhibit Protective Activity Against Oa De...mentioning

confidence: 99%

The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway

Zhou

2023

Front. Endocrinol.

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“…Particularly, in the monolayer culture, which is often the choice for rapid chondrocyte expansion, rapid loss of the primary chondrogenic type of cells is observed. In order to diminish the chondrocyte dedifferentiation, a range of biological stimulants have been tested, which are able to influence the activity of transcription factors or target proteins or to modulate enzymes (COX-2), cytokines (TNF-α/β), and associated inflammatory cascades (NF-kB) that are important for the maintenance of differentiation of chondrocytes [ 2 , 3 , 4 , 5 ]. Moreover, it was found that epigenetic modifications such as DNA methylation of regulatory elements of genes or the histone code are able to determine the chondrocyte’s fate [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Trichostatin A-Mediated Epigenetic Modulation Predominantly Triggers Transcriptomic Alterations in the Ex Vivo Expanded Equine Chondrocytes

Ząbek

Witarski

Szmatoła

et al. 2022

IJMS

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Epigenetic mechanisms of gene regulation are important for the proper differentiation of cells used for therapeutic and regenerative purposes. The primary goal of the present study was to investigate the impacts of 5-aza-2′ deoxycytidine (5-AZA-dc)- and/or trichostatin A (TSA)-mediated approaches applied to epigenomically modulate the ex vivo expanded equine chondrocytes maintained in monolayer culture on the status of chondrogenic cytodifferentiation at the transcriptome level. The results of next-generation sequencing of 3′ mRNA-seq libraries on stimulated and unstimulated chondrocytes of the third passage showed no significant influence of 5-AZA-dc treatment. Chondrocytes stimulated with TSA or with a combination of 5-AZA-dc+TSA revealed significant expressional decline, mainly for genes encoding histone and DNA methyltransferases, but also for other genes, many of which are enriched in canonical pathways that are important for chondrocyte biology. The TSA- or 5-AZA-dc+TSA-induced upregulation of expanded chondrocytes included genes that are involved in histone hyperacetylation and also genes relevant to rheumatoid arthritis and inflammation. Chondrocyte stimulation experiments including a TSA modifier also led to the unexpected expression incrementation of genes encoding HDAC3, SIRT2, and SIRT5 histone deacetylases and the MBD1 CpG-binding domain protein, pointing to another function of the TSA agent besides its epigenetic-like properties. Based on the transcriptomic data, TSA stimulation seems to be undesirable for chondrogenic differentiation of passaged cartilaginous cells in a monolayer culture. Nonetheless, obtained transcriptomic results of TSA-dependent epigenomic modification of the ex vivo expanded equine chondrocytes provide a new source of data important for the potential application of epigenetically altered cells for transplantation purposes in tissue engineering of the equine skeletal system.

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Targeting lysosomal quality control as a therapeutic strategy against aging and diseases

He,

Fan,

Ahmadpoor

et al. 2024

Medicinal Research Reviews

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Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome‐dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

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Potential Methods of Targeting Cellular Aging Hallmarks to Reverse Osteoarthritic Phenotype of Chondrocytes

Cited by 5 publications

References 275 publications

The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway

The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway

Trichostatin A-Mediated Epigenetic Modulation Predominantly Triggers Transcriptomic Alterations in the Ex Vivo Expanded Equine Chondrocytes

Targeting lysosomal quality control as a therapeutic strategy against aging and diseases

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