Abstract：
An imbalanced system of angiogenesis-osteoblasts-osteoclasts is regarded as the main factor in bone remodeling dysfunction diseases or osseointegration loss. Osteoclast precursors are the key cells that accelerate bone-specific angiogenesis and maintain normal osteoblast and osteoclast function. Graphene oxide is an effective scaffold surface modification agent with broad application prospects in bone tissue engineering. However, the effect of graphene oxide on the interaction between osteoclasts and angiogenesis has not yet been elucidated. In this study, a rat calvarial defect model was established and treated with an electrochemically derived nanographene oxide (ENGO) hydrogel. Higher angiogenesis and platelet-derived growth factor (PDGF) B in preosteoclasts were observed in the ENGO group compared with that in the control group. Moreover, in vitro experiments demonstrate the efficacy of ENGO in substantially reducing the expression of the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast-associated markers and inhibiting bone resorption activity. Additionally, ENGO enhances the secretion of the osteoclast-derived coupling factor PDGF-BB and promotes angiogenesis. Our investigation revealed the crucial role of isocitrate dehydrogenase 1 (IDH1) in the ENGO-mediated regulation of osteoclast differentiation and PDGF-BB secretion. The decreased expression of IDH1 reduces the level of histone lysine demethylase 7A (KDM7A) and subsequently increases the H3K9me2 level in the cathepsin K promoter region. In summary, we found that ENGO promotes angiogenesis by inhibiting the maturity of RANKL-induced osteoclasts and enhancing PDGF-BB secretion. These results indicate that ENGO holds promise for the application in fostering osteoclast-endothelial cell crosstalk, providing an effective strategy for treating bone resorption and osteoclast-related bone loss diseases.
摘要：
血管生成-成骨细胞-破骨细胞的不平衡系统被认为是骨重塑功能障碍疾病或骨整合丧失的主要因素。破骨细胞前体是加速骨特异性血管生成和维持正常成骨细胞和破骨细胞功能的关键细胞。氧化石墨烯是一种有效的支架表面改性剂,在骨组织工程中具有广阔的应用前景。然而,氧化石墨烯对破骨细胞与血管生成相互作用的影响尚未阐明。在这项研究中,建立大鼠颅骨缺损模型并用电化学衍生的纳米氧化石墨烯(ENGO)水凝胶处理。与对照组相比，在ENGO组中观察到更高的血管生成和前破骨细胞中的血小板衍生生长因子（PDGF）B。此外，体外实验证明,ENGO能显著降低核因子κB配体(RANKL)诱导的破骨细胞相关标志物受体激活剂的表达,并抑制骨吸收活性.此外,ENGO增强破骨细胞衍生的偶联因子PDGF-BB的分泌并促进血管生成。我们的研究揭示了异柠檬酸脱氢酶1（IDH1）在ENGO介导的破骨细胞分化和PDGF-BB分泌调节中的关键作用。IDH1表达的降低降低了组蛋白赖氨酸脱甲基酶7A（KDM7A）的水平，随后增加了组织蛋白酶K启动子区域中的H3K9me2水平。总之,我们发现ENGO通过抑制RANKL诱导的破骨细胞成熟和促进PDGF-BB分泌促进血管生成。这些结果表明，ENGO有望用于促进破骨细胞-内皮细胞串扰，为骨吸收和破骨细胞相关性骨丢失疾病的治疗提供了有效的策略。
