Effects of mesenchymal stem cells on interleukin-1β-treated chondrocytes and cartilage in a rat osteoarthritic model

Abstract

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.

Evaluation of ALK5 and MMP13 Expression in the Cartilage Tissue of Rats with Osteoarthritis Rats and Effects of Exercise Training, Ozone and Mesenchymal Stem Cell Therapies on Expression of these Genes

“…More recently, Yang et al have demonstrated that treadmill exercise lowers MMP-13 expression in articular cartilage of rats with OA (27). In another study, MSC therapy significantly decreased expression of MMP-13 in rats with knee OA (28). Our findings indicate that exercise training, MSC and ozone therapies are helpful for OA improvement.…”

Cytokine‐induced interleukin‐1 receptor antagonist protein expression in genetically engineered equine mesenchymal stem cells for osteoarthritis treatment

“…Conditioned medium from nontransduced MSC had no protective effect and, instead, the contrary effect was observed, because chondrocytes treated with conditioned medium from stimulated and nonstimulated, nontransduced MSC revealed up‐regulation of IL‐6, IL‐8 and MMP1, as well as down‐regulation of COL2A1 genes. These observations were fairly unexpected because it is known that MSCs secrete factors inhibiting inflammatory processes and a protective effect of MSC co‐cultivated with IL‐1β‐treated chondrocytes in a rat osteoarthritic model was reported recently . We are aware that these expression changes are influenced by several parameters that are closely related to the experimental set‐up (e.g.…”

Protective effects of stem cells from human exfoliated deciduous teeth derived conditioned medium on osteoarthritic chondrocytes

“…Chondrocytes were stimulated with 10 ng/ml of interleukin-1β (Gibco, United States) as previously described [15]. To assess the effect of CM on chondrocyte viability, cells were seeded at a density of 1 × 10 4 cells/cm 2 in 96 well plates (n = 4) and cultured for 48 h. At the end of 48 h, the medium was aspirated and the cells were incubated with DMEM/F-12 supplemented with 0.5% FBS for 12 h to allow the cells to synchronise.…”