IL-1β stimulus determined a significant regulation of survival, apoptotic ratio, as well as of gene expression and serum levels of MMP-1,-3,-13 and Col2a1 in OA chondrocytes compared to baseline.
Furthermore, we evaluated the role of PAR-2 on the synthesis of the major catabolic factors in OA cartilage, including metalloproteinase (MMP)-1 and MMP-13 and the inflammatory mediator cyclooxygenase 2 (COX-2), as well as the PAR-2-activated signalling pathways in OA chondrocytes.
Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5).
Changes in matrix metalloproteinases (MMPs) and apoptosis genes (bax, caspase 3 and tnf-α) and OA-specific protein (MMP-1) expression in vitro and in vivo were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry.
The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients.
FLS from RA and OA that expressed MMP-1, MMP-3, or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express these MMPs (1605, p=0.03; 1970, p=0.004; 2360, p=0.012, respectively).
In this study, we found that silibinin significantly inhibited the nterleukin-1β (IL-1β)-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and IL-6, expression of cyclooxygenase2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5, degradation of aggrecan and collagen-II in human OA chondrocytes.
Our results showed that CS-SM could protect articular cartilage in OA, inhibit the degradation of cartilage, decrease the apoptosis of chondrocytes, decline the content of interleukin-1, tumor necrosis factor-α and Prostaglandins E<sub>2</sub> in synovial fluid, down-regulate the protein expression of matrix metalloproteinase-1 and up-regulate the protein expression of tissue inhibitor of metalloproteinase-1.
Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1β-stimulated human OA chondrocytes.
However, incubation of RA synovial fibroblasts as well as OA synovial fibroblasts with staphylococcal PGs led to an up-regulation of CD54 (ICAM-1) surface expression and to increased expression of MMP-1, MMP-3, and MMP-13 mRNA.
TNF-a stimulation induced IL-6 secretion by RA SFB (3-fold) and OA SFB (4-fold), as well as MMP-1 secretion (RA, 85-fold; OA, 29-fold), with significant differences between RA and OA.
To analyze the in vivo compartmental expression of collagenases 1 and 3 (MMP-1 and MMP-13) in the Hartley guinea pig model of spontaneously occurring osteoarthritis (OA) for the purpose of elucidating their roles in the pathogenesis of OA.
The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients.