Procyanidin B3 prevents articular cartilage degeneration and heterotopic cartilage formation in a mouse surgical osteoarthritis model.
Procyanidin B3 prevents articular cartilage degeneration and heterotopic cartilage formation in a mouse surgical osteoarthritis model.
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DOI：
10.1371/journal.pone.0037728
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Asou Y
中科院分区：
文献类型：
--
作者：
Aini H;Ochi H;Iwata M;Okawa A;Koga D;Okazaki M;Sano A;Asou Y
骨关节炎（OA）是一种常见的疾病，在老年人由于软骨降解和合成的失衡。异位骨化（HO）发生在关节周围软组织内形成异位软骨内骨块时，并由软组织炎症引发。原花青素B3（B3）是一种原花青素二聚体，由于其在人类饮食中的高丰度和抗氧化活性而被广泛研究。在这里，我们评估了从葡萄籽中分离的B3在体外和体内维持软骨细胞中的作用。我们观察到B3抑制H2 O2诱导的原代软骨细胞凋亡，抑制H2 O2或IL-1 β −诱导的一氧化氮合酶（iNOS）产生，并阻止IL-1 β −诱导的原代软骨细胞分化标记基因表达抑制。此外，B3处理增强ATDC 5细胞的早期分化。为了检查B3是否防止体内软骨破坏，在C57 BL/6 J小鼠中手术诱导OA，随后口服给予B3或载体对照。每日口服B3可保护关节软骨免受骨关节炎的影响，并可防止骨关节炎诱导的关节软骨细胞凋亡。此外，B3给药防止了手术区域附近的异位软骨形成。在对照饮食喂养的OA小鼠的滑膜组织和手术区域周围的假包膜中，iNOS蛋白表达增强，但在接受B3的小鼠中减少。总之，这些数据表明，在OA模型中，B3预防OA进展和异位软骨形成，至少部分通过抑制iNOS。这些结果支持B3治疗人OA和异位骨化的潜在治疗获益。
Osteoarthritis (OA) is a common disease in the elderly due to an imbalance in cartilage degradation and synthesis. Heterotopic ossification (HO) occurs when ectopic masses of endochondral bone form within the soft tissues around the joints and is triggered by inflammation of the soft tissues. Procyanidin B3 (B3) is a procyanidin dimer that is widely studied due to its high abundance in the human diet and antioxidant activity. Here, we evaluated the role of B3 isolated from grape seeds in the maintenance of chondrocytes in vitro and in vivo. We observed that B3 inhibited H2O2-induced apoptosis in primary chondrocytes, suppressed H2O2- or IL-1ß−induced nitric oxide synthase (iNOS) production, and prevented IL-1ß−induced suppression of chondrocyte differentiation marker gene expression in primary chondrocytes. Moreover, B3 treatment enhanced the early differentiation of ATDC5 cells. To examine whether B3 prevents cartilage destruction in vivo, OA was surgically induced in C57BL/6J mice followed by oral administration of B3 or vehicle control. Daily oral B3 administration protected articular cartilage from OA and prevented chondrocyte apoptosis in surgically-induced OA joints. Furthermore, B3 administration prevented heterotopic cartilage formation near the surgical region. iNOS protein expression was enhanced in the synovial tissues and the pseudocapsule around the surgical region in OA mice fed a control diet, but was reduced in mice that received B3. Together, these data indicated that in the OA model, B3 prevented OA progression and heterotopic cartilage formation, at least in a part through the suppression of iNOS. These results support the potential therapeutic benefits of B3 for treatment of human OA and heterotopic ossification.
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