The results demonstrated that CH inhibited cell apoptosis, dose‑dependently reduced matrix metalloproteinase (MMP) 13, collagenase and IL‑6 expression, and increased collagen α‑1 (II) chain (COL2A1) expression in human osteoarthritis chondrocytes.
In contrast, COL2A1, other collagen genes, and factors associated with skeletal development were up-regulated in late OA, compared with early OA or normal cartilage.
Our results highlight the contribution of ELF3 to transcriptional regulation of COL2A1 and its potential role in OA disease, and uncover epigenetic mechanisms at play in the regulation of ELF3 and its downstream targets in articular chondrocytes.
Following transfection with ds-miRNA-4784, Col2a1 mRNA expression levels increased by 63 and 126% compared with the levels prior to treatment in groups OA at week 4 and 8, respectively (P<0.01).
Specifically, increased miR-145 levels cause greatly reduced expression of critical cartilage extracellular matrix genes (COL2A1 and aggrecan) and tissue-specific microRNAs (miR-675 and miR-140) and increased levels of the hypertrophic markers RUNX2 and MMP13, characteristic of changes occurring in osteoarthritis.
In grades II and III OA cartilage, the expression of miR-146a and COL2A1 was decreased, whereas the expression of matrix metalloproteinase 13 (MMP-13) was elevated in grade II OA cartilage.
Compared with the normal group, the expression of ALK1, SMAD1, COL10A1 and MMP3 was higher in the OA groups, whereas the expression of COL2A1 was lower in the OA groups.
There was a significant decrease in aggrecan and type II collagen (COL2A1) gene expressions by 73% (p = 0.029) and 65% (p = 0.029), respectively, in advanced OA area compared with the minimally OA area.
A significant correlation was, however, observed for H19, COL2A1, and miR-675 expression levels in OA tissue, and functional regulation of these candidate molecules was assessed under anabolic and catabolic conditions.
Viral transduction of LOXL2 in OA chondrocytes increased the mRNA levels of chondroitin sulfate proteoglycan (CSPG4), aggrecan (ACAN), sex determining region Y-box containing gene 9 (SOX9), and COL2A1 but reduced the levels of extracellular matrix (ECM)-degrading enzymes matrix metalloproteinase (MMP)1, MMP3, and MMP13.
RESULTS Icariin treatment (mice in the ACLT + ICA group) significantly reduced degeneration of cartilage in OA with increased cartilage thickness, associated with increased expression of collagen type II alpha 1 (COL2A1), decreased chondrocyte hypertrophy, and decreased expression of collagen type X (ColX) and matrix metalloproteinase 13 (MMP13).
While H-PRP showed similar effects on expression of chondrogenic markers (Col2a1 and Sox9) as the negative control group (p > 0.05), OA-PRP decreased chondrocyte expression of Col2a1 and Sox-9 messenger RNA by 40% and 30%, respectively (Col2a1, p = 0.015; Sox9, p = 0.037).
In this present study, we used IL-1β (10 ng/ml) to mimic OA chondrocytes and we found that IL-1β stimulated chondrocytes caused the increasing expression of ADAMTS5 and MMP13, decreasing COL2A1 expression, which were in accord with OA chondrocytes changes.
Compared to control group, increasing levels of β-catenin and MMP-13 expression with reduction of miR-320 and COL2A1 expressions were observed in OA chondrocytes.
Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1.