Ferrándiz María Luisa, Terencio María Carmen, Carceller María Carmen, Ruhí Ramón, Dalmau Pere, Vergés Josep, Montell Eulàlia, Torrent Anna, Alcaraz María José
Department of Pharmacology and IDM, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain.
Technological Extraction Department, BIOIBERICA S.A., Pol. Ind. "Mas Puigvert", Crta. N-II, Km 680.6, 08389, Palafolls, Barcelona, Spain.
BMC Musculoskelet Disord. 2015 Apr 17;16:92. doi: 10.1186/s12891-015-0547-9.
Osteoarthritis (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.
We 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.
Oral 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.
We 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.
骨关节炎（OA）是最常见的关节疾病，也是导致残疾的主要原因。需要有效的治疗方法来减缓疾病进展。一些现有的治疗方法是提供天然成分的膳食补充剂。最近的研究表明，雌激素缺乏会导致OA进展的病理生理事件。
我们使用去卵巢大鼠的前交叉韧带横断OA模型，研究了BIS076的作用，BIS076是一种与羟基磷灰石（作为钙源）和维生素D3相关的天然猪软骨提取物的新制剂。通过组织化学跟踪软骨降解、蛋白聚糖消耗和滑膜炎。通过μCT确定对骨微结构的影响。通过Luminex或ELISA测量血清中生物标志物的水平和膝关节匀浆中炎症介质的水平。
口服BIS076可减少关节软骨损伤以及软骨降解标志物II型胶原C末端肽、软骨寡聚基质蛋白和基质金属蛋白酶-3的血清水平。BIS076下调了局部炎症反应，关节组织中促炎细胞因子和前列腺素E2的产生减少。此外，BIS076对干骺端骨改变有效，因为该制剂增加了骨体积密度并改善了骨微结构。这些作用与骨代谢的改变有关，骨生物标志物的变化反映了这一点，核因子κB受体活化因子配体/骨保护素的比值以及抗酒石酸酸性磷酸酶-5b的水平降低，表明BIS076对小梁骨吸收具有抑制活性。
我们已经证明了一种新制剂（BIS076）在去卵巢大鼠OA实验模型中对关节病变和骨改变的保护作用。本研究支持BIS076在OA治疗中的应用价值。
