Excessive degradation of type II collagen and aggrecan by matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS) induced by AGEs is a pivotal event in the pathogenesis of osteoarthritis.
In the present study, we identified that cyanidin treatment could strongly suppress the expression of NO, PGE2, TNF-α, IL-6, iNOs, COX-2, ADAMTS5 and MMP13, and reduce the degradation of aggrecan and collagen II in IL-1β-induced human OA chondrocytes, indicating the anti-inflammatory effect of cyanidin.
Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA.
Preventative treatments against the destruction of type II collagen and aggrecan, the two main components of the articular extracellular matrix, may serve as a novel therapy against the progression of OA.
CONCLUSIONS These results indicate that the effects of XG are related to the Wnt3a/ß-catenin pathway and XG suppresses matrix degradation by inhibiting the expression of MMPs and ADAMTS and promotes aggrecan and collagen II content in the ECM, indicating its favorable potential for use in OA therapy.
HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA.
Abnormal loss of components of the extracellular matrix (ECM) including type II collagen and aggrecan caused by proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) is an important pathophysiological characteristic of osteoarthritis (OA).
Mechanistic studies have shown that knockdown of SUMO2/3 expression can significantly enhance the rate of degradation of aggrecan and collagen type II at both the mRNA and protein levels in the OA model.
Upon chondrogenic induction, OA-MSC underwent rapid chondrogenesis in comparison to BMSC as shown by Alcian blue staining and activation of ACAN and COL2A1 gene expression.
DC32 upregulated the mRNA expression of Type II collagen and aggrecan, and downregulated the mRNA expression of MMP2, MMP3, MMP13 and ADAMTS-5 in the knee joints of papain-induced OA mice measured by qPCR.
In addition, the effect of intra-articularly injected WY14643 on articular cartilage in a mouse OA model established by the destabilization of the medial meniscus was assessed using the Osteoarthritis Research Society International (OARSI) histopathology assessment system, along with the detection of Aggrecan, ADAMTS5, LC3B and P62 protein levels using immunohistochemistry assay.
The quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of LINC01534, aggrecan, collagen II, and matrix metalloproteinase (MMPs) in OA cartilage tissue or OA chondrocyte model induced by IL-1β.
Joint destruction resulting from excessive degradation of type II collagen and aggrecan in the articular extracellular matrix by metalloproteinases and aggrecanases, respectively, is a major pathological hallmark of osteoarthritis.
Aggrecanase-2 (ADAMTS5) gene is responsible for aggrecan degradation that may contribute to cartilage destruction in a mouse osteoarthritis (OA) model.
The levels of miR-23b-3p were upregulated, while the expressions of collagen II and aggrecan were decreased in OA tissues and in IL-1β-treated CHON-001 cells.
Therefore, understanding the mechanisms that control the expression of type II collagen and aggrecan would be useful for understanding gene expression changes in diseases such as osteoarthritis.
A locked nucleic acid (LNA)-anti-miR-449a increased cartilage regeneration and expression of type II collagen and aggrecan on the regenerated cartilage surface in acute defect and OA models.
Moreover, PDRN decreased expression of metalloproteinase 13, as a catabolic factor for OA, but increased expression of aggrecan, which was an anabolic factor for OA.
The ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) enzyme is a matrix-associated zinc metalloendopeptidase that plays an essential role in the degradation of cartilage aggrecan in arthritic diseases and has been recognized as one of the most primary targets for therapeutic intervention in osteoarthritis (OA).
Deficient PSMD11, associated with reduced phosphorylated FOXO4, promotes impaired proteasomal function in OA chondrocytes, dysregulation of chondrocytic homeostasis, and decreased levels of SOX9 mRNA, SOX9 protein, and AGC1 mRNA.
In this study, we found that phloretin significantly inhibited the IL-1β-induced production of NO, PGE2, TNF-α, and IL-6, the expression of COX-2, iNOS, MMP-3, MMP-13, and ADAMTS-5, and the degradation of aggrecan and collagen-II in human OA chondrocytes.
MSC-Exos increased chondrogenic genes Col2a1 (type II collagen alpha 1) and aggrecan, decreased hondrocyte hypertrophy markers MMP-13 (matrix metalloproteinase-13) and Runx2 (runt-related transcription factor 2) in chondrocytes isolated from OA model mice.