Osteoarthritis (OA), one of the most common joint disease, affects more than 80% of the population aged 70 or over. Mesenchymal stem cells (MSCs) show multi-potent differentiation and self-renewal capability, and, after exposure to an inflammatory environment, also exhibit immunosuppressive properties. In this study, we have used a model of lipopolysaccharide (LPS)-stimulated chondrocytes to evaluate MSC anti-inflammatory efficacy. The anti-inflammatory mechanism was tested in two cell-contained culture systems: (i) MSC-chondrocyte indirect contact system and (ii) MSC-chondrocyte direct contact system, and one cytokine-only culture system: MSC-conditioned medium (CM) system. Results showed that MSCs reduced chondrocyte inflammation through both paracrine secretion and cell-to-cell contact. The inflammation-associated, and free-radical-related genes were down-regulated significantly in the direct contact system on 24 h, however, the TNF-α. IL-6 were upregulated and aggrecan, COLII were downregulated on 72 h in direct contact system. Moreover, we found CM produced by MSC possess well therapeutic effect on inflammatory chondorcyte, and the 10-fold concentrated MSC-conditioned medium could down-regulated chondorcyte synthesis inflammation-associated, and free-radical-related genes, such as TNF-α, IL-1β, IL-6 and iNOS even treated for 72 h. In conclusion, MSC-CM showed great potential for MSC-based therapy for OA.
1 October 2018 in Journal of the Taiwan Institute of Chemical Engineers
Due to the limitation in the current treatment modalities, such as secondary surgery in ACI and fibrocartilage formation in microfracture surgery, various scaffolds or hydrogels have been developed for cartilage regeneration. In the present study, we used sodium periodate to oxidize methylcellulose and formed dialdehyde methylcellulose (DAC) after dialysis and freeze-drying process, DAC was further mixed with succinyl-chitosan (SUC) to form an DAC-SUC in situ forming hydrogel. The hydrogel is a stiffness, elastic-like and porous hydrogel according to the observation of SEM and rheological analysis. DAC-SUC13 hydrogel possess well cell-compatibility as well as biodegradability. Most bone marrow mesenchymal stem cells (BM-pMSCs) were alive in the hydrogel and possess chondrogenesis potential. According to the results of animal study, we found DAC-SUC13 hydrogel can function as a stem cell carrier to promote glycosaminoglycans and type II collagen synthesis in the osteochondral defects of porcine knee. These findings suggested that DAC-SUC13 hydrogel combined with stem cell is a potential treatment for cartilage defects repair in the future.
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone remodeling, leading to chronic pain and reduced mobility. In early-stage OA, sustained oxidative stress and inflammation drive chondrocyte dysfunction and extracellular matrix (ECM) loss. Hyaluronic acid (HA), a key component of synovial fluid responsible for lubrication and viscoelasticity, is prone to enzymatic and oxidative degradation under inflammatory conditions, limiting its therapeutic effect. To address this, we developed an HA-based system incorporating the natural antioxidant and anti-inflammatory molecule carvacrol. The potential of this formulation was assessed in interleukin-1b-stimulated chondrocytes, which mimic the inflammatory environment of OA. The carvacrol-added HA combination upregulated antioxidant enzyme expression, attenuated pro-inflammatory signaling, and promoted ECM preservation by up regulating cartilage-specific markers and glycosaminoglycan production. In vivo efficacy was further evaluated in a rat model of monosodium iodoacetate-induced OA. HA-Carvacrol treatment alleviated pain-related behaviors and preserved cartilage structure, as confirmed by behavioral assessments and histological analyses. This dual-function formulation integrates the lubricating benefits of HA with the bioactivity of carvacrol, providing preclinical proof-of-concept evidence for its potential in early-stage OA.
Oxidation is a significant contributor to inflammatory responses. However, the association between antioxidant capacity and anti-inflammatory capacity of antioxidants is unclear. This study investigated the correlation between antioxidant capacity and anti-inflammatory capacity for six common standard antioxidants, namely myricetin, eriodictyol, luteolin, kaempferol, apigenin, and quercetin. The abilities of these antioxidants to scavenge DPPH, ABTS, superoxide, and hydroxyl radicals and the anti-inflammatory capacities of these antioxidants against proinflammatory mediators TNF-α, IL-6, IL-1β, and nitric oxide were examined using a cellular inflammation model. Multivariable regression analysis was employed to quantitatively assess the mathematical relationship between antioxidant and anti-inflammatory capacities. The results suggested that antioxidant capacity may serve as a preliminary indicator of anti-inflammatory capacity for TNF-α (adjusted R 2 = 0.999, p < 0.01), IL-6 (adjusted R 2 = 0.958, p < 0.05), and nitric oxide (adjusted R 2 = 0.955, p < 0.05). However, the anti-inflammatory capacity models varied with antioxidant capacity tests. Significant explanatory power was not demonstrated for the IL-1β model, suggesting limitations in predicting the anti-inflammatory capacity of certain mediators. Simple antioxidant capacity tests are promising for predicting complex anti-inflammatory capacity. However, further research is necessary to elucidate the complex mechanisms underlying inflammation and the efficacy of antioxidants in mitigating inflammation.