The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

Silent mating type information regulation 2 homolog 1 (SIRT1) has been reported to inhibit osteoarthritic gene expression in chondrocytes. Here, efforts in this study were made to unveil the specific role of SIRT1 in the therapy of acupuncture on cartilage degeneration in osteoarthritis (OA). Specifically, OA was established by the anterior cruciate ligament transection method in the right knee joint of rats, subsequent to which acupuncture was performed on two acupoints. Injection with shSIRT1 sequence–inserted lentiviruses was conducted to investigate the role of SIRT1 in acupuncture-mediated OA. Morphological changes and cell apoptosis in rat OA cartilages were examined by safranin-O staining and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay, respectively. The serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-2 in OA rats were assessed by enzyme-linked immunosorbent assay (ELISA). The expressions of SIRT1, cartilage matrix degradation-related proteins (matrix metalloproteinase (MMP)-9 and ADAMTS5), NF-κB signaling-related markers (p-p65/p65 and p-IκBα/IκBα), and cartilage matrix synthesis-related proteins (collagen II and aggrecan) in the OA cartilage were analyzed by western blot. As a result, acupuncture counteracted OA-associated upregulation of TNF-α, IL-2, cartilage matrix degradation-related proteins, and NF-κB signaling-related markers, morphological damage, apoptosis, SIRT1 downregulation, and loss of cartilage matrix synthesis-related proteins in rat articular cartilages. SIRT1 silencing reversed acupuncture-induced counteractive effects on the aforementioned OA-associated phenomena (except apoptosis, the experiment regarding which under SIRT1 silencing was not performed). Collectively, acupuncture inhibited chondrocyte apoptosis, inflammation, NF-κB signaling activation, and cartilage matrix degradation by upregulating SIRT1 expression to delay OA-associated cartilage degeneration.

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LncRNA MALAT1/MiR-145 Adjusts IL-1β-Induced Chondrocytes Viability and Cartilage Matrix Degradation by Regulating ADAMTS5 in Human Osteoarthritis

Yonsei Medical Journal ◽

10.3349/ymj.2019.60.11.1081 ◽

2019 ◽

Vol 60 (11) ◽

pp. 1081 ◽

Cited By ~ 8

Author(s):

Chengyao Liu ◽

Shan Ren ◽

Shifeng Zhao ◽

Yandong Wang

Keyword(s):

Cartilage Matrix ◽

Matrix Degradation ◽

Lncrna Malat1 ◽

And Cartilage

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Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.760988 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaopeng Song ◽

Tianwen Ma ◽

Hailong Hu ◽

Mingchao Zhao ◽

Hui Bai ◽

...

Keyword(s):

Circadian Rhythm ◽

Signaling Pathway ◽

Early Stage ◽

Cruciate Ligament ◽

Cartilage Degeneration ◽

Matrix Degradation ◽

Knee Cartilage ◽

Rhythm Disturbance ◽

Gsk 3Β ◽

Canonical Wnt

With the gradual deepening of understanding of systemic health and quality of life, the factors affecting osteoarthritis (OA) are not limited to mechanical injury, metabolic abnormality, age and obesity, etc., but circadian rhythm, which plays a non-negligible role in human daily life. The purpose of this study was to explore the molecular mechanism of chronic circadian rhythm disturbance (CRD) inducing cartilage OA-like degeneration. Rats with the anterior cruciate ligament excision transection (ACLT) were used to establish the early-stage OA model (6-week). The light/dark (LD) cycle shifted 12 h per week for 22 weeks in order to establish a chronic CRD model. BMAL1 knockdown (KD) and Wnt/β-catenin pathway inhibition were performed in chondrocytes. The contents of proinflammatory factors and OA biomarkers in serum and chondrocyte secretions were detected by ELISA. Pathological and immunohistochemical staining of articular cartilage indicated the deterioration of cartilage. WB and qPCR were used to evaluate the relationship between matrix degradation and the activation of Wnt/β-catenin signaling pathway in chondrocytes. We found that chronic CRD could cause OA-like pathological changes in knee cartilage of rats, accelerating cartilage matrix degradation and synovial inflammation. The expression of MMP-3, MMP-13, ADAMTS-4, and β-catenin increased significantly; BMAL1, Aggrecan, and COL2A1 decreased significantly in either LD-shifted cartilage or BMAL1-KD chondrocytes. The expression of β-catenin and p-GSK-3β elevated, while p-β-catenin and GSK-3β diminished. The inhibitor XAV-939 was able to mitigated the increased inflammation produced by transfected siBMAL1. Our study demonstrates that chronic CRD disrupts the balance of matrix synthesis and catabolic metabolism in cartilage and chondrocytes, and it is related to the activation of the canonical Wnt/β-catenin signaling pathway.

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Honokiol, a low molecular weight natural product, prevents inflammatory response and cartilage matrix degradation in human osteoarthritis chondrocytes

Journal of Orthopaedic Research® ◽

10.1002/jor.22577 ◽

2013 ◽

Vol 32 (4) ◽

pp. 573-580 ◽

Cited By ~ 42

Author(s):

Ying Ju Chen ◽

Keh Sung Tsai ◽

Ding Cheng Chan ◽

Kuo Cheng Lan ◽

Cheng Feng Chen ◽

...

Keyword(s):

Molecular Weight ◽

Inflammatory Response ◽

Natural Product ◽

Cartilage Matrix ◽

Low Molecular Weight ◽

Matrix Degradation ◽

Osteoarthritis Chondrocytes ◽

And Cartilage

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miR-211 Reduces the Degradation of Articular Cartilage Matrix by Targeting Matrix Metalloproteninase 9

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2136 ◽

2019 ◽

Vol 9 (9) ◽

pp. 1292-1297

Author(s):

Yumei Tian ◽

Jian Wang

Keyword(s):

Cartilage Damage ◽

Cartilage Matrix ◽

Cartilage Tissue ◽

Control Group ◽

Matrix Degradation ◽

Mankin Score ◽

Joint Cavity ◽

Mmp9 Expression ◽

Col2a1 Expression ◽

And Cartilage

Matrix metalloproteninase 9 (MMP9) promotes osteoarthritis (OA) cartilage matrix degradation. Abnormal miR-211 expression is associated with OA. Bioinformatics analysis showed a targeted relationship between miR-211 and MMP9 mRNA 3′-UTR. Our study intends to evaluate miR-211’s role in the destruction of chondrocyte matrix in OA model rats. The OA model rats were divided into OA group, OA group+agomir-NC group, OA group+agomir-211 group, followed by analysis of the arthritis Mankin score, Hyp and IL-1β content by ELISA, MMP-9 and COL2A1 expression by western blot and miR-211 level by qRT-PCR. The cartilage tissues were divided into control group, IL-1β+ agomir-NC group, IL-1β+ agomir-211 group, and the expression of MMP-9 and COL2A1 in chondrocytes were detected. Compared with Sham group, IL-1β and Hyp levels in the joint cavity fluid of the OA group were significantly increased and miR-211 expression was significantly decreased with increased MMP9 expression and decreased COL2A1 expression. Injection of agomir-211 into the joint cavity of OA rats significantly reduced MMP9 expression in cartilage tissue, decreased Hyp content in the joint cavity fluid, increased COL2A1 expression, and decreased Mankin score and cartilage damage. IL-1β treatment significantly up-regulated MMP9 expression and decreased COL2A1 expression; miR-211 overexpression attenuated IL-1β-induced cartilage matrix degradation and cartilage destruction. miR-211 plays a role in regulating MMP9 expression and promoting OA. miR-211 overexpression inhibits MMP9 expression, reduces the degradation of cartilage matrix and increases collagen synthesis, thus ameliorating OA development.

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