IL-6, IL-1β and TNF-α regulation of the chondrocyte phenotype: a possible mechanism of haemophilic cartilage destruction

Zheng, Liujie; Han, Zhiwei; Luo, Dasheng; Li, Jiale; Pang, Nanyu; Ding, Mingyang; Ye, Houlong; Zhu, Kun Yan; Yao, Yunfeng

doi:10.1080/16078454.2023.2179867

Cited by 7 publications

(2 citation statements)

References 29 publications

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“…We then detected much lower phosphorylation level of AKT in Tnxb-KD chondrocytes and HA models. These results are in line with previous report showing that the expression of p-AKT1 was down-regulated in the articular cartilage of patients with HA compared with that in patients with OA 58 . Notably, we further demonstrated that AKT agonist effectively restored the abnormal Mmp13 expression and apoptosis induced by Tnxb knockdown.…”

Section: Discussionsupporting

confidence: 93%

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

Chen,

Qinghe,

Wang

et al. 2023

Preprint

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BackgroudRecurrent joint bleeding in hemophilia patients frequently results in hemophilic arthropathy (HA). Drastic degradation of articular cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. Here, we conducted a genome-wide DNA methylation study with the goal of identifying critical genes for HA cartilage degeneration.MethodsDNA was isolated from human osteoarthritis (N = 5) and HA (N = 5) articular cartilages and analyzed using the Infinium Human Methylation 850 BeadChip array. Adeno-associated virus-mediated shRNA and siRNA were used to knock down Tenascin XB (TNXB)in vivoandin vitro, respectively. Then histopathological analysis, qPCR, Western blotting and immunofluorescence assays were conducted to detected chondrocyte homeostasis and HA progression.ResultsWe found that DNMT1 and DNMT3A protein levels were increased in cartilages from HA patients compared with OA patients. Genome-wide DNA methylation analysis identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses then revealed that DMR genes (DMGs) were related to extracellular matrix organization. Among these DMGs, TNXB protein expression was down-regulated in human and mouse HA cartilages. Further, the loss ofTnxbin F8−/−mouse cartilage provides a disease-promoting role in HA by augmenting cartilage matrix degeneration and subchondral bone loss.Tnxbknockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed a chondroprotective effect followingTnxbknockdown.Conclusionsour study demonstrated that TNXB is a central mediator of cartilage matrix degradation following joint bleeding, which functions by regulating the activation of AKT. These mechanistic insights allow targeted development of potentially new strategies for cartilage protection in HA.

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Section: Discussionsupporting

confidence: 93%

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

Chen,

Qinghe,

Wang

et al. 2023

Preprint

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“…As shown in Figure 1, these molecules promote cartilage degradation, inhibit cartilage repair, and contribute to joint pain and stiffness. Levels of several pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), are increased in the synovial fluid and joint tissues of individuals with OA [32][33][34]. In healthy joints, there is a balance between proinflammatory and anti-inflammatory cytokines.…”

Section: Inflammation and Oamentioning

confidence: 99%

A Review of Cyclic Phosphatidic Acid and Other Potential Therapeutic Targets for Treating Osteoarthritis

Tsukahara,

Imamura,

Morohoshi

2023

Biomedicines

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Osteoarthritis (OA), a chronic degenerative joint disease, is the most common form of arthritis. OA occurs when the protective cartilage that cushions the ends of bones gradually breaks down. This leads to the rubbing of bones against each other, resulting in pain and stiffness. Cyclic phosphatidic acid (cPA) shows promise as a treatment for OA. In this article, we review the most recent findings regarding the biological functions of cPA signaling in mammalian systems, specifically in relation to OA. cPA is a naturally occurring phospholipid mediator with unique cyclic phosphate rings at the sn-2 and sn-3 positions in the glycerol backbone. cPA promotes various responses, including cell proliferation, migration, and survival. cPA possesses physiological activities that are distinct from those elicited by lysophosphatidic acid; however, its biochemical origin has rarely been studied. Although there is currently no cure for OA, advances in medical research may lead to new therapies or strategies in the future, and cPA has potential therapeutic applications.

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The effect of Abrus cantoniensis Hance on liver damage in mice

Li,

Tu,

Dai

et al. 2023

Ecotoxicology and Environmental Safety

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IL-6, IL-1β and TNF-α regulation of the chondrocyte phenotype: a possible mechanism of haemophilic cartilage destruction

Cited by 7 publications

References 29 publications

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

Aberrant methylation and expression of TNXB promote chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

A Review of Cyclic Phosphatidic Acid and Other Potential Therapeutic Targets for Treating Osteoarthritis

The effect of Abrus cantoniensis Hance on liver damage in mice

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