a Department of Biochemistry and Molecular Dentistry , and.
b Department of Orthodontics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.
Mod Rheumatol. 2016 Nov;26(6):940-949. doi: 10.3109/14397595.2016.1155255. Epub 2016 Apr 21.
Platelet-rich plasma (PRP) has been widely used to enhance the regeneration of damaged joint tissues, such as osteoarthritic and rheumatoid arthritic cartilage. The aim of this study is to clarify the involvement of all of the CCN family proteins that are crucially associated with joint tissue regeneration.
Cyr61-CTGF-NOV (CCN) family proteins in human platelets and megakaryocytic cells were comprehensively analyzed by Western blotting analysis. Production of CCN family proteins in megakaryocytes in vivo was confirmed by immunofluorescence analysis of mouse bone marrow cells. Effects of CCN family proteins found in platelets on chondrocytes were evaluated by using human chondrocytic HCS-2/8 cells.
Inclusion of CCN2, a mesenchymal tissue regenerator, was confirmed. Of note, CCN3, which counteracts CCN2, was newly found to be encapsulated in platelets. Interestingly, these two family members were not detectable in megakaryocytic cells, but their external origins were suggested. Furthermore, we found for the first time CCN5 and CCN1 that inhibits ADAMTS4 in both platelets and megakaryocytes. Finally, application of a CCN family cocktail mimicking platelets onto HCS-2/8 cells enhanced their chondrocytic phenotype.
Multiple inclusion of CCN1, 2 and 3 in platelets was clarified, which supports the harmonized regenerative potential of PRP in joint therapeutics.
富含血小板的血浆（PRP）已被广泛用于增强受损关节组织的再生，如骨关节炎和类风湿关节炎软骨。本研究旨在阐明与关节组织再生密切相关的所有 CCN 家族蛋白的参与情况。
通过 Western blot 分析全面分析了人血小板和巨核细胞中的 Cyr61-CTGF-NOV（CCN）家族蛋白。通过免疫荧光分析小鼠骨髓细胞，证实了巨核细胞中 CCN 家族蛋白的产生。通过使用人软骨细胞 HCS-2/8 细胞评估血小板中发现的 CCN 家族蛋白对软骨细胞的影响。
包含间充质组织再生剂 CCN2 得到了证实。值得注意的是，新发现的与 CCN2 对抗的 CCN3 被包裹在血小板中。有趣的是，这两个家族成员在巨核细胞中无法检测到，但提示它们有外部来源。此外，我们首次发现 CCN5 和 CCN1 在血小板和巨核细胞中均抑制 ADAMTS4。最后，将模仿血小板的 CCN 家族鸡尾酒应用于 HCS-2/8 细胞增强了其软骨细胞表型。
明确了 CCN1、2 和 3 在血小板中的多重包含，这支持了 PRP 在关节治疗中的协调再生潜力。
