Osteoarthritis (OA) is a chronic, painful, degenerative and inflammatory disease that affects the synovial joints and leads finally to the loss of mobility. It is highly prevalent in dogs. Nowadays, no cure exists, and the pharmacological treatment is limited to clinical signs alleviation. Some positive beneficial effects have been highlighted with dietary supplements in the course of dog OA. The goals of this narrative review are to summarize the scientific data available in the literature on dietary supplements assessed in dog OA and to discuss some trails about how to improve several aspects of research and issues with dietary supplements, such as bioavailability and dosage regimen. Chondroitin sulphate, glucosamine, undenaturated type II collagen, avocado-soya bean unsaponifiables, curcumin and polyunsaturated fatty acids were studied in dog OA and therefore discussed in the present review. Most of them showed anticatabolic and anti-inflammatory effects. Unfortunately, few data exist concerning their pharmacokinetics. Their bioavailability is low, but new formulations are developed to enhance their gastrointestinal absorption. The clinical relevance of these new formulations compared to native forms should be demonstrated in good clinical trials. Even if further investigations are needed, dietary supplements should be considered in OA management.
Oleuropein and rutin ± curcumin significantly slowed down the progression of spontaneous OA lesions in guinea pigs. While no additive effect was seen in the curcumin + rutin group, the differential effects of oleuropein and rutin on inflammatory and cartilage catabolic markers suggest an interesting combination for future studies in OA protection.
ObjectiveOsteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone.DesignSecretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients. Finally, osteomodulin and fibulin-3 sequences were quantified by western blot and immunoassays in serum and culture supernatants.Results175 proteins were identified in NSC osteoblast secretome. Data are available via ProteomeXchange with identifier PXD008494. Compared to NSC osteoblast secretome, 12 proteins were significantly less secreted (Osteomodulin, IGFBP5, VCAM-1, IGF2, 78 kDa glucose-regulated protein, versican, calumenin, IGFBP2, thrombospondin-4, periostin, reticulocalbin 1 and osteonectin), and 13 proteins were significantly more secreted by SC osteoblasts (CHI3L1, fibulin-3, SERPINE2, IGFBP6, SH3BGRL3, SERPINE1, reticulocalbin3, alpha-2-HS-glycoprotein, TIMP-2, IGFBP3, TIMP-1, SERPINF1, CSF-1). Similar changes in osteomodulin, IGF2, SERPINE1, fibulin-3 and CHI3L1 mRNA levels were observed. ELISAs assays confirm the decrease by half of osteomodulin protein in SC osteoblasts supernatant compared to NSC and in OA patients serum compared to healthy subjects. Fibulin-3 epitopes Fib3-1, Fib3-2 and Fib3-3 were also increased in SC osteoblasts supernatant compared to NSC.ConclusionsWe highlighted some proteins differentially secreted by the osteoblasts coming from OA subchondral bone sclerosis. These changes contribute to explain some features observed in OA subchondral bone, like the increase of bone remodeling or abnormalities in bone matrix mineralization. Among identified proteins, osteomodulin was found decreased and fibulin-3 increased in serum of OA patients. These findings suggest that osteomodulin and fibulin-3 fragments could be biomarkers to monitor early changes in subchondral bone metabolism in OA.
The main objective of this study was to assess the in vitro effects of curcuminoids extract, hydrolyzed collagen and green tea extract in normal bovine chondrocytes and osteoarthritic human chondrocytes cultured in monolayer. This study also investigated the synergic or additive effects of these compounds. Enzymatically isolated primary bovine or human chondrocytes were cultured in monolayer until confluence and then incubated for 24 hours or 48 hours in the absence or in the presence of interleukin-1β and with or without curcuminoids extract, hydrolyzed collagen or green tea extract, added alone or in combination, at different concentrations. Cell viability was neither affected by these compounds, nor by interleukin 1β. In the absence of interleukin-1β, compounds did not significantly affect bovine chondrocytes metabolism. In human chondrocytes and in the absence of interleukin 1β, curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract significantly inhibited matrix metalloproteinase-3 production. In interleukin-1β-stimulated bovine chondrocytes, interleukin-6, inducible nitric oxide synthase, cyclooxygenase2, matrix metalloproteinase 3, a disintegrin and metalloproteinase with thrombospondin type I motifs 4 and a disintegrin and metalloproteinase with thrombospondin type I motifs 5 expressions were decreased by curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract. The combination of the three compounds was significantly more efficient to inhibit interleukin-1β stimulated matrix metalloproteinase-3 expression than curcuminoids extract alone. In interleukin-1β-stimulated human chondrocytes, nitric oxide, interleukin-6 and matrix metalloproteinase 3 productions were significantly reduced by curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract. These findings indicate that a mixture of curcuminoids extract, hydrolyzed collagen and green tea extract has beneficial effects on chondrocytes culture in inflammatory conditions and provide a preclinical basis for the in vivo testing of this mixture.
Osteoarthritis (OA) is a painful, degenerative and inflammatory disease that affects the entire synovial joints. Nowadays, no cure exists, and the pharmacological treatments are limited to symptoms alleviation. There is a need for a new efficient and safe treatment. Viscosupplementation is a process that aims to restore the normal rheological properties of synovial fluid. For the past years, hyaluronic acid was usually used but this molecule has some limitations including the short residency time in joint cavity. Recently, in vitro studies have suggested that chitosan could promote the expression of cartilage matrix components and reduce inflammatory and catabolic mediator's production by chondrocytes. In vivo, chitosan prevented cartilage degradation and synovial membrane inflammation in OA induced rabbit model. Several studies have also shown that chitosan could induce chondrogenic differentiation of mesenchymal stem cells. Therefore, chitosan is an interesting polymer to design scaffold and hydrogel for cartilage lesion repair, cells transplantation, sustained drug release and viscosupplementation.
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