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BackgroundOsteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. There is a need for effective treatments able to slow the progression of disease. Some of the available treatments are dietary supplements providing natural components. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression.MethodsWe have used the anterior cruciate ligament transection model of OA in ovariectomised rats to study the effects of BIS076, a new formulation of a natural porcine cartilage extract associated with hydroxyapatite (as a source of calcium) and vitamin D3. Cartilage degradation, proteoglycan depletion and synovitis were followed by histochemistry. Effects on bone microstructure were determined by μCT. The levels of biomarkers in serum and inflammatory mediators in knee homogenates were measured by luminex or ELISA.ResultsOral administration of BIS076 reduced articular cartilage damage and serum levels of cartilage degradation markers C-telopeptide of type II collagen and cartilage oligomeric matrix protein, as well as matrix metalloproteinase-3. The local inflammatory response was down-regulated by BIS076 with lower production of pro-inflammatory cytokines and prostaglandin E2 in joint tissues. In addition, BIS076 was effective on metaphyseal bone alterations as this formulation increased volumetric bone mineral density and improved bone micro-architecture. These effects were related to the modification of bone metabolism reflected by changes in bone biomarkers with reductions in the ratio receptor activator of nuclear factor κB ligand/osteoprotegerin and the levels of tartrate-resistant acid phosphatase-5b, suggesting an inhibitory activity of BIS076 on trabecular bone resorption.ConclusionsWe have demonstrated the protective properties of a new formulation (BIS076) on joint lesion and bone alterations in an experimental model of OA in ovariectomised rats. This study supports the interest of BIS076 in OA treatments.

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Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

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