In the present study, the effects and mechanisms of mesenchymal stem cells (MSCs) on interleukin (IL)-1β-stimulated rat chondrocytes, as well as cartilage from a rat model of osteoarthritis (OA) induced by anterior cruciate ligament transection and medial meniscectomy were investigated. Confluent rat chondrocytes were treated with IL-1β (10 ng/ml), then cultured indirectly with or without MSCs at a ratio of 2:1. Total RNA and protein were collected at various time-points, and western blot and reverse transcription-quantitative polymerase chain reaction analyses were used to investigate the expression of type II collagen (Col2), aggrecan, matrix metalloproteinase-13 (MMP-13) and cyclooxygenase-2 (COX-2). The activation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) p65 and inhibitory-κ-B-α (IκBα) were also assessed by western blotting. In addition, the in vivo effects of MSCs in a rat OA model were assessed by histology and western blot analysis. The results indicated that in vitro, IL-1β markedly upregulated the expression of MMP-13, COX-2, phosphorylated ERK1/2, JNK, p38 MAPK and NF-κB p65, and inhibited the expression of Col2, aggrecan and IκBα. Conversely, MSCs enhanced the expression of Col2, aggrecan and IκBα, and inhibited the expression of MMP-13 and NF-κB p65 in IL-1β-stimulated rat chondrocytes. In vivo histological and western blot analyses revealed analogous results to the in vitro findings. The results of the present study demonstrated that MSCs suppressed the inflammatory response and extracellular matrix degradation in IL-1β-induced rat chondrocytes, as well as cartilage in a osteoarthritic rat model, in part via the NF-κB signaling pathway.
We sought to compare the preventive effects of mitomycin-C(MMC) and chitosan on intraarticular adhesion after knee surgery in rabbits. For this purpose, 48 New-Zealand rabbits were randomly and equally divided into MMC, chitosan, and control groups. Approximately 10 × 10 mm(2) of the cortical bone was removed from both sides of left femoral condyle and the cancellous bone underneath was exposed. The decorticated areas were topically treated with MMC and chitosan while control group was treated with physiological saline. The lower left limb was fixed in flexed position with Kirschner-wire for 4 weeks postoperatively. After 4 weeks, gross and histopathological examination, biochemical analysis, and fibroblast counts were performed on knee intraarticular adhesion in each group. The data show mild membrane-like fibrous intraarticular adhesion, presented in loose, in MMC group. There was moderate intraarticular adhesion in chitosan group while in controls; there was large-size compact fibrous tissue adhesion. Hydroxyproline contents and fibroblast quantity of MMC and chitosan groups were lower (P < 0.05) than that of control group. We, therefore, concluded that MMC and chitosan could prevent intraarticular adhesion of the knee in rabbits by inhibiting fibroblast proliferation and reducing collagenous fiber formation while MMC had a better preventive effect than that of chitosan.
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