Abstract
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.
Highlights
Osteoarthritis (OA) is the most frequent articular disease and a leading cause of disability
Effect of BIS076 on histopathological changes in the joint The histopathological analysis showed the presence of cartilage damage in Control rats (Figures 1 and 2)
The grade of cartilage damage in the groups treated with BIS076 (T1 and T2) was bone volume (BV)/TV(%) BS/TV(mm−1)
Summary
Osteoarthritis (OA) is the most frequent articular disease and a leading cause of disability. Recent studies have shown that estrogen deficiency contributes to the pathophysiological events of OA progression. Both osteoarthritis (OA) and osteoporosis are major public health problems affecting hundreds of millions of people. Disability related to these conditions is expected to rise as a result of population aging [1,2]. Recent studies have revealed several factors which contribute to the pathogenesis of both disorders such as subchondral bone loss or inflammation [9]. Antiresorptive drugs have shown positive effects on bone changes and cartilage destruction in OA [16,17]
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