Platelets promote cartilage repair and chondrocyte proliferation via ADP in a rodent model of osteoarthritis
Platelets promote cartilage repair and chondrocyte proliferation via ADP in a rodent model of osteoarthritis
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在啮齿动物骨关节炎模型中，血小板通过 ADP 促进软骨修复和软骨细胞增殖
DOI：
10.3109/09537104.2015.1075493
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发表时间：
2016-04-02
期刊：
影响因子：
3.3
通讯作者：
Hu, Hu
中科院分区：
文献类型：
--
作者：
Zhou, Qi;Xu, Chunhua;Hu, Hu
摘要骨关节炎(OA)是最常见的与年龄相关的退行性关节疾病，富含血小板血浆(PRP)已被证明对其有益。因此，在本研究中，我们旨在探讨血小板对软骨细胞的影响及其机制。与血小板共培养后，测定软骨细胞的合成代谢和分解代谢活性及增殖率。实时荧光定量聚合酶链式反应检测软骨细胞基因表达。免疫印迹法检测软骨细胞蛋白表达和磷酸化水平。将经或不经血小板处理的软骨细胞移植到大鼠关节腔内注射碘乙酸单钠诱导的骨性关节炎模型中，对关节软骨的修复进行大体和组织学评价。血小板显著促进软骨细胞的增殖，但对合成代谢和分解代谢活性影响不大。与血小板共培养的软骨细胞显示骨形态发生蛋白7(BMP7)的产生显著增加。BMP7的自分泌/旁分泌作用通过ERK/CDK1/Cyclin B1信号通路促进软骨细胞的增殖。在OA模型中，经血小板处理的软骨细胞移植显示出更好的软骨修复。血小板来源的ADP是通过ADP受体P2Y1促进BMP7的产生和软骨细胞增殖的主要介质。最后，将α，β-亚甲基腺苷-5‘-二磷酸直接注射到骨性关节炎关节也能促进软骨修复。这项研究已经证实，在骨关节炎中，血小板源性ADP而不是ATP是促进血小板促进的软骨细胞增殖和软骨修复的关键介质。这一发现可能为血小板在骨性关节炎中的治疗效果提供一个关键的解释，并有助于形成改善骨性关节炎治疗的策略。
Abstract Osteoarthritis (OA) is the most common age-related degenerative joint disease and platelet-rich plasma (PRP) has been shown to be beneficial in OA. Therefore, in this study, we aimed to investigate the effects of platelets on chondrocytes and the underlying mechanisms. Anabolic and catabolic activity and the proliferation rate of chondrocytes were evaluated after co-culture with platelets. Chondrocyte gene expression was measured by real-time PCR. Chondrocyte protein expression and phosphorylation were measured by western blot. Chondrocytes treated with or without platelets were transplanted into a rat model of OA induced by intra-articular injection of monosodium iodoacetate and the repair of articular cartilage was evaluated macroscopically and histologically. Platelets significantly promoted the proliferation of chondrocytes, while mildly influencing anabolic and catabolic activity. Chondrocytes co-cultured with platelets showed significantly increased production of bone morphogenetic protein 7 (BMP7). The autocrine/paracrine effect of BMP7 was responsible for the increased proliferation of chondrocytes, via the ERK/CDK1/cyclin B1 signaling pathway. Transplantation of platelet-treated chondrocytes showed better cartilage repair in the OA model. Platelet-derived ADP was identified as the major mediator to promote the production of BMP7 and the proliferation of chondrocytes, through the ADP receptor P2Y1. Finally, direct injection of α,β-methyleneadenosine-5′-diphosphate into OA joints also enhanced cartilage repair. This study has identified that platelet-derived ADP, but not ATP, is the key mediator for platelet-promoted chondrocyte proliferation and cartilage repair in osteoarthritis. This finding may provide a key explanation for the therapeutic effect of platelets in OA and help shaping a strategy to improve OA therapy.