Vitamin K2 Ameliorates Damage of Blood Vessels by Glucocorticoid: a Potential Mechanism for Its Protective Effects in Glucocorticoid-induced Osteonecrosis of the Femoral Head in a Rat Model.
Vitamin K2 Ameliorates Damage of Blood Vessels by Glucocorticoid: a Potential Mechanism for Its Protective Effects in Glucocorticoid-induced Osteonecrosis of the Femoral Head in a Rat Model.
复制标题
DOI：
10.7150/ijbs.15248
复制
发表时间：
2016
影响因子：
9.2
通讯作者：
Gao YS
中科院分区：
文献类型：
--
作者：
Zhang Y;Yin J;Ding H;Zhang C;Gao YS
据报道，糖皮质激素会减少血管数量并损害股骨头的血液供应，这被认为是糖皮质激素引起股骨头坏死（ONFH）的重要机制。为了预防糖皮质激素诱发的 ONFH，促进骨形成和血管生成的药物将是理想的选择。维生素 K2 已被证明在骨代谢中发挥着重要作用；然而，很少有研究关注维生素 K2 对新血管形成的影响。因此，本研究旨在调查维生素 K2 在体外和体内糖皮质激素存在下是否促进新血管形成。阐明了维生素 K2 对在有或没有地塞米松孵育的 EAhy926 中的活力、迁移、体外管形成以及 VEGF、vWF、CD31、KDR、Flt 和 PDGFB 的影响。在 MG63 成骨细胞样细胞系中也检测到 VEGF、TGF-β 和 BMP-2（成骨细胞分泌的血管生成相关蛋白）。此外，使用血管造影和 CD31 染色评估给予或不给予甲泼尼龙和维生素 K2 的大鼠股骨头血管。体外研究表明，维生素 K2 显着保护内皮细胞免受地塞米松诱导的细胞凋亡，促进内皮细胞迁移和体外管形成。当与地塞米松共同处理时，维生素 K2 也会上调 EAhy926 和 MG63 中的血管生成相关蛋白。体内研究表明，与仅用甲基泼尼松龙治疗的大鼠相比，用 VK2 和甲基泼尼松龙联合治疗的大鼠的血管体积和 CD31 阳性染色细胞有所增强。总的来说，维生素 K2 能够在体外促进血管生成，并在体内改善糖皮质激素治疗大鼠的股骨头血管，这表明维生素 K2 是一种有前途的药物，可用于预防类固醇诱导的 ONFH。
Glucocorticoid has been reported to decrease blood vessel number and harm the blood supply in the femoral head, which is recognized to be an important mechanism of glucocorticoid-induced osteonecrosis of the femoral head (ONFH). To prevent glucocorticoid-induced ONFH, medication that promotes both bone formation and angiogenesis would be ideal. Vitamin K2 has been revealed to play an important role in bone metabolism; however, few studies have focused on the effect of Vitamin K2 on new vascular formation. Thus, this study aimed to investigate whether Vitamin K2 promoted new blood vessel formation in the presence of glucocorticoids, both in vitro and in vivo. The effect of Vitamin K2 on viability, migration, in vitro tube formation, and VEGF, vWF, CD31, KDR, Flt and PDGFB in EAhy926 incubated with or without dexamethasone were elucidated. VEGF, TGF-β and BMP-2, angiogenesis-related proteins secreted by osteoblasts, were also detected in the osteoblast-like cell line of MG63. In addition, blood vessels of the femoral head in rats administered with or without methylprednisolone and Vitamin K2 were evaluated using angiography and CD31 staining. In vitro studies showed that Vitamin K2 significantly protected endothelial cells from dexamethasone-induced apoptosis, promoted endothelial cell migration and in vitro tube formation. Angiogenesis-related proteins both in EAhy926 and MG63 were also upregulated by Vitamin K2 when cotreated with dexamethasone. In vivo studies showed enhanced blood vessel volume and CD31-positive staining cells in rats cotreated with VK2 and methylprednisolone compared to rats treated with methylprednisolone only. Collectively, Vitamin K2 has the ability to promote angiogenesis in vitro and to ameliorate vessels of the femoral head in glucocorticoid-treated rats in vivo, indicating that Vitamin K2 is a promising drug that may be used to prevent steroid-induced ONFH.