The Role of Autophagy in Osteoarthritis

Duan, Ran; Xie, Hui; Liu, Zhengzhao

doi:10.3389/fcell.2020.608388

Cited by 100 publications

(87 citation statements)

References 95 publications

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“…It maintains organelle and protein functions and attenuates the detrimental stress during cell apoptosis (Choi et al, 2013). Existing evidence has suggested that autophagy is suppressed in OA (Shapiro et al, 2014;Zhang et al, 2015) and recovers the function of injured chondrocytes (Duan et al, 2020). According to our screening work, integrin β4 (ITGB4) was identified as a differentially expressed gene (DEG) in OA and is related to autophagy.…”

Section: Introductionmentioning

confidence: 94%

Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway

Sun

Zheng

Liu

et al. 2021

Front. Mol. Biosci.

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Background: Osteoarthritis (OA) is one of the most common degenerative joint diseases characterized by increased apoptosis and autophagy deficiency. The investigation was performed to examine the effect of valproic acid (VPA) and molecular mechanism related to miR-302d-3p/ITGB4 axis in OA.Methods: The OA clinical samples were obtained from the GEO database to analyze differentially expressed genes. An in vitro OA model was mimicked by LPS in CHON-001 cells. Autophagy-related genes were downloaded from the HADb website, and potential drugs were mined using the CTD website. The upstream factors of ITGB4 were predicted with bioinformatics analysis, which was validated by luciferase activity assay and RIP assay. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry. The expression levels, including ITGB4, miR-302d-3p, and autophagy-/PI3K-AKT pathway-related markers, were measured by qRT-PCR or/and western blot.Results: Our results showed that miR-302d-3p inhibited cell viability and promoted apoptosis of LPS-treated CHON-001 cells by targeting ITGB4. VPA treatment remarkably alleviated LPS-stimulated injury in CHON-001 cells. The inhibitory effect of VPA on LPS-stimulated damage in CHON-001 cells was weakened by miR-302d-3p overexpression, while it was intensified because of ITGB4 upregulation. Mechanistically, VPA treatment induced a significant decrease in the levels of p-PI3K and p-AKT in LPS-stimulated CHON-001 cells through regulating miR-302d-3p/ITGB4 axis.Conclusion: Overall, VPA treatment may ameliorate LPS-induced injury on chondrocytes via the regulation of miR-302d-3p/ITGB4 pair and the inactivation of the PI3K-AKT pathway.

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Section: Introductionmentioning

confidence: 94%

Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway

Sun

Zheng

Liu

et al. 2021

Front. Mol. Biosci.

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“…Usually, a mechanical load or inflammatory cytokines are applied to cells in order to mimic OA conditions. In particular, OA mimic conditions are applied to cells growing in a monolayer, in a scaffold or in a co-culture system [ 62 ]. The use of 3D cell models may represent a good alternative to 2D cultures.…”

Section: In Vitro and In Vivo Models For Oa Studiesmentioning

confidence: 99%

Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies

Valenti

Carbonare

Zipeto

et al. 2021

IJMS

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Autophagy is involved in different degenerative diseases and it may control epigenetic modifications, metabolic processes, stem cells differentiation as well as apoptosis. Autophagy plays a key role in maintaining the homeostasis of cartilage, the tissue produced by chondrocytes; its impairment has been associated to cartilage dysfunctions such as osteoarthritis (OA). Due to their location in a reduced oxygen context, both differentiating and mature chondrocytes are at risk of premature apoptosis, which can be prevented by autophagy. AutophagomiRNAs, which regulate the autophagic process, have been found differentially expressed in OA. AutophagomiRNAs, as well as other regulatory molecules, may also be useful as therapeutic targets. In this review, we describe and discuss the role of autophagy in OA, focusing mainly on the control of autophagomiRNAs in OA pathogenesis and their potential therapeutic applications.

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“…Osteoarthritis (OA) is a common degenerative disorder of the joints that accounts for major physical pain in older adults [ 1 , 2 ]. OA could result in severe joint pain, stiffness, limited motion, disability, and in serious cases, the loss of joint mobility [ 3 , 4 ]. OA is regarded as the leading cause of lower limb disability, with a disability rate of up to 53% [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Liu

et al. 2021

J Nanobiotechnol

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Background Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration. However, few studies reported their potential in the development of osteoarthritis (OA) previously. In this study, we explored the biological roles and underlying mechanism of MSCs-EVs in OA. Results Co-culture experiments revealed that MSCs-EVs could promote the expression of collagen type II alpha 1 chain (COL2A1), SRY-box transcription factor 9 (SOX9) and Aggrecan while negatively regulate the expression of chondrocyte hypertrophy markers matrix metallopeptidase 13 (MMP-13) and RUNX family transcription factor 2 (Runx2) in mouse chondrocytes in the OA model. Besides, the results of cell experiments indicated that MSCs-EVs could notably weaken the suppression of chondrocyte proliferation, migration and the promotion of chondrocyte apoptosis via interleukin1β (IL-1β) induction. In addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1β-induced chondrocyte injury. Mechanistically, we elucidated that circHIPK3 could directly bind to miR-124-3p and subsequently elevate the expression of the target gene MYH9. Conclusion The findings in our study demonstrated that EVs-circHIPK3 participated in MSCs-EVs-mediated chondrocyte proliferation and migration induction and in chondrocyte apoptosis inhibition via the miR-124-3p/MYH9 axis. This offers a promising novel cell-free therapy for treating OA. Graphic abstract

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The Role of Autophagy in Osteoarthritis

Cited by 100 publications

References 95 publications

Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway

Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway

Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies

Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

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