PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes

Chen, Xiaolei; Chen, Ri; Xu, Yang; Xia, Chun

doi:10.1002/2211-5463.13064

Cited by 7 publications

(5 citation statements)

References 57 publications

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“…The immunofluorescence experiments, using an anti‐PI‐PLC γ1 antibody, recognizing an epitope mapping at the C‐terminal of the protein, show a significant decrease of PI‐PLC γ1. The decreased of this protein seems desirable in OA, previously has been described that the inhibition of PI‐PLC γ1 stimulates the production of ECM in rat chondrocytes challenged with proinflammatory cytokine IL‐1β 35 . Moreover, the intra‐articular injection of PI‐PLC γ1 inhibitor in rat OA joint showed a decrease of PI‐PLC γ1 phosphorylation level, giving a protective action on chondrocytes 36 .…”

Section: Discussionmentioning

confidence: 94%

“…The decreased of this protein seems desirable in OA, previously has been described that the inhibition of PI-PLC γ1 stimulates the production of ECM in rat chondrocytes challenged with proinflammatory cytokine IL-1β. 35 Moreover, the intra-articular injection of PI-PLC γ1 inhibitor in rat OA joint showed a decrease of PI-PLC γ1 phosphorylation level, giving a protective action on chondrocytes. 36 In our context, the decreased amount of protein means a lower amount of active PI-PLC γ1 enzyme, which results in a protective action in OA.…”

Section: Discussionmentioning

confidence: 97%

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Intron retention in PI‐PLC γ1 mRNA as a key mechanism affecting MMP expression in human primary fibroblast‐like synovial cells

Mariano,

Ammendola,

Migliorini

et al. 2024

Cell Biochemistry & Function

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The intron retention (IR) is a phenomenon utilized by cells to allow diverse fates at the same mRNA, leading to a different pattern of synthesis of the same protein. In this study, we analyzed the modulation of phosphoinositide‐specific phospholipase C (PI‐PLC) enzymes by Harpagophytum procumbens extract (HPE) in synoviocytes from joins of osteoarthritis (OA) patients. In some samples, the PI‐PLC γ1 isoform mature mRNA showed the IR and, in these synoviocytes, the HPE treatment increased the phenomenon. Moreover, we highlighted that as a consequence of IR, a lower amount of PI‐PLC γ1 was produced. The decrease of PI‐PLC γ1 was associated with the decrease of metalloprotease‐3 (MMP‐3), and MMP‐13, and ADAMTS‐5 after HPE treatment. The altered expression of MMPs is a hallmark of the onset and progression of OA, thus substances able to decrease their expression are very desirable. The interesting outcomes of this study are that 35% of analyzed synovial tissues showed the IR phenomenon in the PI‐PLC γ1 mRNA and that the HPE treatment increased this phenomenon. For the first time, we found that the decrease of PI‐PLC γ1 protein in synoviocytes interferes with MMP production, thus affecting the pathways involved in the MMP expression. This finding was validated by the silencing of PI‐PLC γ1 in synoviocytes where the IR phenomenon was not present. Our results shed new light on the biochemical mechanisms involved in the degrading enzyme production in the joint of OA patients, suggesting a new therapeutic target and highlighting the importance of personalized medicine.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Intron retention in PI‐PLC γ1 mRNA as a key mechanism affecting MMP expression in human primary fibroblast‐like synovial cells

Mariano,

Ammendola,

Migliorini

et al. 2024

Cell Biochemistry & Function

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“…Increasing ROS level was detected in chondrocytes with PUM2 overexpression in our experiments. It has been reported that the excessive accumulation of ROS represents the intracellular oxidative stress, and maybe mediate IL-1β-induced cell apoptosis of chondrocytes [ 33 , 34 ]. Oxidative stress has been demonstrated to participate in the impairment of chondrocytes [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

RNA binding protein PUM2 promotes IL-1β-induced apoptosis of chondrocytes via regulating FOXO3 expression

Wang,

Zhang,

et al. 2024

Heliyon

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“…If we further relate our findings to those from other studies with respect to fibroblasts and epithelial cells, we are apparently publishing pioneering work on how Z-VAD affects cell viability and the inflammatory response to TNFα. Most research is focused on inflammation-induced cell viability and ROS production, for which Z-VAD was found to increase the sensitivity of L929 [ 41 ] and rat chondrocytes [ 42 ] to inflammatory clues. In our study, TNFα alone or in combination with Z-VAD had no negative impact on the metabolic activity of fibroblastic cells.…”

Section: Discussionmentioning

confidence: 99%

Blocking of Caspases Exerts Anti-Inflammatory Effects on Periodontal Cells

Panahipour

Cervantes

Abbasabadi

et al. 2022

Life

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Periodontitis is an inflammatory process that is associated with caspase activity. Caspases could thus become molecular targets for the modulation of the inflammatory response to harmful factors, such as lipopolysaccharides (LPS) and TNFα. Here, the impact of the pan-caspase inhibitor Z-VAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoro-methyl ketone) on the modulation of the LPS-induced inflammatory response of murine RAW 264.7 cells and primary macrophages was examined. Moreover, the inflammatory responses of human gingival fibroblasts, HSC2 oral squamous carcinoma cells and murine ST2 mesenchymal fibroblasts when exposed to TNFα were studied. Data showed that Z-VAD-FMK significantly lowered the inflammatory response of RAW 264.7 cells and primary macrophages, as indicated by the expression of IL1 and IL6. In murine ST2 mesenchymal fibroblasts, the TNFα-induced expression of CCL2 and CCL5 was significantly reduced. In human gingival fibroblasts and HSC2 cells, Z-VAD-FMK considerably reduced the TNFα-induced expression of CXCL8 and CXCL10. These findings suggest that pharmacological blocking of caspases in an inflammatory environment lowers the expression of cytokines and chemokines in periodontal cells.

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PLCγ1 inhibition combined with inhibition of apoptosis and necroptosis increases cartilage matrix synthesis in IL‐1β‐treated rat chondrocytes

Cited by 7 publications

References 57 publications

Intron retention in PI‐PLC γ1 mRNA as a key mechanism affecting MMP expression in human primary fibroblast‐like synovial cells

Intron retention in PI‐PLC γ1 mRNA as a key mechanism affecting MMP expression in human primary fibroblast‐like synovial cells

RNA binding protein PUM2 promotes IL-1β-induced apoptosis of chondrocytes via regulating FOXO3 expression

Blocking of Caspases Exerts Anti-Inflammatory Effects on Periodontal Cells

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