Di Cesare Mannelli Lorenzo, Micheli Laura, Zanardelli Matteo, Ghelardini Carla
BMC Musculoskelet Disord. 2013 Aug 1;14:228. doi: 10.1186/1471-2474-14-228.
Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA).
1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 13 days starting from the day of MIA intra-articular injection.
On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage.
These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage.
骨关节炎是最常见的关节疾病。骨关节炎患者会经历疼痛和行动能力受损，导致生活质量显著下降。进行性软骨损失导致疾病不断发展且难以治疗。慢性疾病的特点决定了需要新的疾病缓解活性药物。本研究的目的是评估低剂量天然II型胶原蛋白在单碘乙酸钠（MIA）诱导的大鼠骨关节炎模型中的作用。
从关节内注射MIA当天开始，每天口服给予1、3和10mg/kg猪天然II型胶原蛋白，持续13天。
在第14天，胶原蛋白治疗的大鼠显示出对MIA诱导的疼痛阈值改变有显著预防作用。使用机械性有害刺激（爪压力试验）或非有害刺激（电子von Frey试验）对爪子进行评估，并直接在受损关节上测量关节疼痛的减轻（PAM试验）。胶原蛋白减轻疼痛的效果随着剂量降低而增强。此外，观察到以 hind limb weight bearing alterations（失能试验）衡量的姿势失衡减少，以及运动活动的总体改善（Animex试验）。最后，软骨降解生物标志物II型胶原交联C末端肽（CTX-II）的血浆和尿液水平降低，表明结构性关节损伤有胶原蛋白依赖性降低。
这些结果描述了低剂量天然II型胶原蛋白作为止痛药的临床前疗效，其机制涉及对软骨的保护作用。
