AdipoRon在改善糖尿病患者牙种植体骨整合能力的相关机制研究

糖尿病是影响种植治疗成功的危险因素之一，高血糖会上调脂肪组织内巨噬细胞促炎因子TNF-alpha的分泌，影响骨细胞的功能，进而影响种植体-骨界面的骨整合，因此患者血糖控制不佳会影响种植治疗效果。我们前期研究发现，TNF-alpha会导致软骨工程骨的吸收，即种植体周骨吸收。有文献报道脂联素能有效抑制巨噬细胞促炎因子TNF-alpha的分泌、抑制破骨分化、促进成骨分化，但因种种原因，脂联素不适临床使用。AdipoRon，一种可以口服的脂联素受体激动剂，可有效降低饮食诱导肥胖动物的血糖水平，有很大的临床使用前景。然AdipoRon对糖尿病患者种植体骨整合影响尚未知。因此，我们提出假说：AdipoRon能通过抑制促炎因子的释放，促进成骨、抑制破骨从而改善糖尿病患者的牙种植体骨整合能力。本研究拟从分子、细胞和动物水平验证该假说，为提高糖尿病患者种植体骨整合能力提供新途径。

Diabetes is considered as one of the risk factors for dental implant therapy. Hyperglycemia leads to increased secretion of TNF-alpha in macrophages in white adipose tissues, down-regulateing bone cell biology and thus decreases the osseointegration of the implant-bone interface. Our previous studies showed that TNF-alpha caused bone resorption in tissue-engineered cartilage, and shall lead to peri-implant bone resorption. Adiponectin is effective in inhibiting the secretion of proinflammatory cytokines like TNF-alpha, down-regulating osteoclastogenesis, promoting osteogenesis, while it is not suitable for clinical application. AdipoRon, an oral adiponectin receptor agonist, effectively in reducing plasma glucose in diet-induced obesity mice, has potential in clinical use. However, the effects of AdipoRon on osseointegration in patients with diabetes are unknown. Thus, hypothesis is proposed that AdipoRon can improve the osseointegration of dental implants in diabetic patients by promoting osteogenesis, inhibiting osteoclastogenesis, and decrease the secretion of proinflammatory cytokines. We intend to validate our hypothesis by using various kinds of techniques as bioinformatics analysis, protein co-immunoprecipitation and RNA interferences and provide new avenues for improving the osseointegration of dental implant in diabetic patients.