Targeting regulated chondrocyte death in osteoarthritis therapy

Zhu, Rendi; Wang, Qianqian; Ouyang, Ziwei; Hao, Wen‐Juan; Zhou, Fuli; Yan, Lin; Cheng, Yuanzhi; Zhou, Ren‐Peng; Hu, Wei

doi:10.1016/j.bcp.2023.115707

Cited by 18 publications

(4 citation statements)

References 183 publications

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“…Increased chondrocyte apoptosis is a key manifestation of OA. In advanced-stage OA, chondrocytes become sparse and form cavities, and the ECM is also reduced due to chondrocyte apoptosis ( 25 ). It has been confirmed that in OA cartilage tissue, the apoptotic rate of chondrocytes is ~20% ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis

Chen,

Fu,

Jie

et al. 2024

Mol Med Rep

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During osteoarthritis (OA), chondrocytes become highly active, with increased matrix synthesis and inflammatory cytokine-induced catabolic pathways. Early intervention strategies targeting pathological changes may attenuate or halt disease progression. The present study aimed to reveal the role of glutathione peroxidase (GPX)7 in OA. For this purpose, a research model was established by inducing C28/I2 human chondrocytes with interleukin (IL)-1β, and the expression level of GPX7 was determined. To explore its roles, C28/I2 cells were transfected to gain GPX7 overexpression. The effects of GPX7 overexpression on intracellular inflammation, extracellular matrix (ECM) degradation, apoptosis and ferroptosis were then evaluated. In addition, the cells were treated with the ferroptosis inducer, erastin, and its effects on the aforementioned phenotypes were assessed. The level of GPX7 was decreased in response to IL-1β treatment, and GPX7 overexpression suppressed cellular inflammation, ECM degradation and apoptosis. Moreover, the reduction of lipid peroxidation, ferrous ions and transferrin indicated that GPX7 overexpression inhibited ferroptosis. Subsequently, inflammation, ECM degradation and apoptosis were found to be promoted in the cells upon treatment with erastin. These findings suggested that the regulatory role of GPX7 may be mediated by a pathway involving ferroptosis. On the whole, the present study revealed that GPX7 reduces IL-1β-induced chondrocyte inflammation, apoptosis and ECM degradation partially through a mechanism involving ferroptosis. The results of the present study lay a theoretical foundation for subsequent OA-related research and may enable the development of translational strategies for the treatment of OA.

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Section: Discussionmentioning

confidence: 99%

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis

Chen,

Fu,

Jie

et al. 2024

Mol Med Rep

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“…GO analysis revealed that DEGs are predominantly associated to endochondral ossification and ECM degradation, recognized as pivotal contributors to OA pathogenesis [ 26 ]. The mechanism may involve chondrocyte apoptosis [ 27 ], KEGG results also showed that DEGs were significantly enriched in ferroptosis pathway. In addition, our findings indicate a significant correlation between PDE activity and OA.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel potential drugs for the treatment and prevention of osteoarthritis

Han,

Bai,

et al. 2024

Biochemistry and Biophysics Reports

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“…Given that these strategies are primarily tailored for the treatment of localized cartilage injuries, the future of regenerative medicine holds the potential to expand its scope to address degenerative cartilage conditions like osteoarthritis. In such conditions, cellular senescence plays a pivotal role in the breakdown of the extracellular matrix and tissue deterioration [ 55 , 56 ]. Cellular senescence is a complex process that halts cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Cartilage Defect Treatment Using High-Density Autologous Chondrocyte Implantation (HD-ACI)

Guillén-García,

Guillén-Vicente,

Rodríguez-Iñigo

et al. 2023

Bioengineering

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Hyaline cartilage’s inability to self-repair can lead to osteoarthritis and joint replacement. Various treatments, including cell therapy, have been developed for cartilage damage. Autologous chondrocyte implantation (ACI) is considered the best option for focal chondral lesions. In this article, we aimed to create a narrative review that highlights the evolution and enhancement of our chondrocyte implantation technique: High-Density-ACI (HD-ACI) Membrane-assisted Autologous Chondrocyte Implantation (MACI) improved ACI using a collagen membrane as a carrier. However, low cell density in MACI resulted in softer regenerated tissue. HD-ACI was developed to improve MACI, implanting 5 million chondrocytes per cm2, providing higher cell density. In animal models, HD-ACI formed hyaline-like cartilage, while other treatments led to fibrocartilage. HD-ACI was further evaluated in patients with knee or ankle defects and expanded to treat hip lesions and bilateral defects. HD-ACI offers a potential solution for cartilage defects, improving outcomes in regenerative medicine and cell therapy. HD-ACI, with its higher cell density, shows promise for treating chondral defects and advancing cartilage repair in regenerative medicine and cell therapy.

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Targeting regulated chondrocyte death in osteoarthritis therapy

Cited by 18 publications

References 183 publications

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL‑1β, via a mechanism mediated by ferroptosis

Identification of novel potential drugs for the treatment and prevention of osteoarthritis

Cartilage Defect Treatment Using High-Density Autologous Chondrocyte Implantation (HD-ACI)

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