Punicalin alleviates TNF‐α‐ and IL‐1β‐induced chondrocyte dysfunction and cartilage metabolism via mediating FOXO3 signaling axis

Objective The present study aims to assess for temporal changes in tibial subchondral bone and cartilage in WNIN/Gr-Ob rats (portraying obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, hypertension) in comparison with Wistar controls (WNIN) using anthropometry, micro-computed tomography (micro-CT), scanning electron microscopy (SEM), histopathology, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Design Body weight, abdominal circumference, body mass index (BMI), lean/fat mass, serum tumor necrosis factor (TNF)-α levels were measured (ELISA), followed by ultrastructural analysis of tibial subchondral bone (micro-CT) and cartilage architecture (histopathology and SEM) in WNIN/Gr-Ob and WNIN rats with age (3, 6 and 9 months). Additionally, primary cultures of articular chondrocytes isolated from 6-month-old WNIN/Gr-Ob and WNIN rats were assessed for matrix metalloproteinase (MMP)-13 and Collagen type II (COL2A1) by immunofluorescence. Results WNIN/Gr-Ob rats exhibited frank obesity with increased BMI, lean and fat mass vis-à-vis significantly higher levels of serum TNF-α (6>9>3 months) as compared with the controls. With an increase in BMI, WNIN/Gr-Ob rats presented with tibial cartilage fibrillation, erosion, osteophyte formation (6 months) and subchondral bone cyst (9 months) confirmed by histology and SEM. An increase in subchondral trabecular bone volume (sclerosis with decreased plate porosity) was observed in all ages in WNIN/Gr-Ob rats compared to their Control. Gaining insights, primary cultures of articular chondrocytes complemented with altered cellular expressions of COL2A1 and MMP-13 from WNIN/Gr-Ob rats, indicating osteoarthritis (OA) progression. Conclusion Multiple metabolic perturbations featured in WNIN/Gr-Ob rats were effective to induce spontaneous OA-like degenerative changes affecting knee joints akin to human OA.

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Docetaxel-triggered SIDT2/NOX4/JNK/HuR signaling axis is associated with TNF-α-mediated apoptosis of cancer cells

Biochemical Pharmacology ◽

10.1016/j.bcp.2021.114865 ◽

2021 ◽

pp. 114865

Author(s):

Liang-Jun Wang ◽

Jing-Ting Chiou ◽

Yuan-Chin Lee ◽

Long-Sen Chang

Keyword(s):

Cancer Cells ◽

Tnf Α ◽

Signaling Axis

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EphB4/ TNFR2/ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation

BMC Molecular and Cell Biology ◽

10.1186/s12860-020-00273-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Yu Zhang ◽

Chengzhe Yang ◽

Shaohua Ge ◽

Limei Wang ◽

Jin Zhang ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Signaling Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Erk Mapk ◽

Tnf Α ◽

Signaling Axis ◽

Positive Effect

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Diurnal Variation in the Response of the Mandible to Orthopedic Force

Journal of Dental Research ◽

10.1177/154405910208101011 ◽

2002 ◽

Vol 81 (10) ◽

pp. 711-715 ◽

Cited By ~ 14

Author(s):

S. Yamada ◽

S. Saeki ◽

I. Takahashi ◽

K. Igarashi ◽

H. Shinoda ◽

...

Keyword(s):

Diurnal Variation ◽

Dark Period ◽

Time Of Day ◽

Light Period ◽

Considerable Reduction ◽

Cartilage Metabolism ◽

Differentiation And Proliferation ◽

And Cartilage

Bone and cartilage metabolism is known to be more active during rest than during periods of activity. The purpose of this study was to examine the hypothesis that mandibular retractive force could be more effective when applied to rats during rest. Mandibular retractive force caused a considerable reduction in the condylar length in experimental groups, and the magnitude of this reduction was greater in the Light-period (08:00-20:00) group than in the Dark-period (20:00-08:00) group. The differentiation and proliferation of chondrocytes were inhibited in animals in the Light-period group, compared with those in the Dark-period group. These results suggest that the orthopedic effects of mandibular retractive force vary depending on the time of day the force is applied, and that such force may be more effective while animals are resting than while they are active.

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PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-019-1394-4 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 5

Author(s):

Songyang Liu ◽

Chenxi Cao ◽

Yujun Zhang ◽

Guangyu Liu ◽

Weixia Ren ◽

...

Keyword(s):

Cartilage Damage ◽

Inhibitory Effect ◽

Pi3k Inhibitor ◽

Akt Pathway ◽

Akt Inhibitor ◽

Pi3k Inhibitor Ly294002 ◽

Tnf Α ◽

Invasive Capacity ◽

And Cartilage ◽

Fibroblast Like Synoviocytes

Abstract Background The Cadherin-11 and PI3K/Akt pathway are increasingly recognized as the potential therapeutic target of osteoarthritis (OA) synovitis. The study aimed to investigate the role of PI3K/Akt signaling pathway in the expression of Cadherin-11 and migration and invasive capacity of fibroblast-like synoviocytes (FLS) of OA patients under stimulation of TNF-α and to explore the effect of the PI3K/Akt inhibitor and Cadherin-11 antibody in the therapy of the collagenase-induced osteoarthritis (CIOA) mice. Methods FLS were primarily cultured from synovium of osteoarthritic patients during total knee arthroplasty. Under the simulation of TNF-α, with or without PI3K/Akt inhibitor LY294002, Cadherin-11 expression was detected by real-time PCR and Western blot, as well as the migration and invasive capacity changes of OA FLS. Cadherin-11 antibody was injected intraarticularly or LY294002 was injected intraperitoneally in CIOA mice to evaluate the changes of synovitis score, cartilage damage, and Cadherin-11 expression. Results TNF-α stimulation increased Cadherin-11 expression at mRNA and protein level in OA FLS and also increased the phosphorylation-dependent activation of Akt. PI3K inhibitor LY294002 attenuated TNF-α-induced overexpression of Cadherin-11 and decreased the invasive capacity of OA FLS. Intraperitoneal injection of PI3K inhibitor LY294002 could decrease the Cadherin-11 protein expression in synovium of CIOA mice, although it has no significant inhibitory effect on synovitis and cartilage damage. Intraarticular injection of Cadherin-11 antibody attenuated the synovitis and cartilage damage in the CIOA joints and decreased Cadherin-11 expression in the synovial lining. Conclusions PI3K/Akt pathway was associated with TNF-α-induced activation of OA FLS, which may involve in the pathogenesis of osteoarthritis. Anti-Cadherin-11 therapy in CIOA mice could attenuate the pathological changes of OA joints.

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