Alpha-ketoglutarate up-regulates autophagic activity in peri-implant environment and enhances dental implant osseointegration in osteoporotic mice

被引:11
|
作者
Liu, Ruojing [1 ,2 ]
Gao, Yi [3 ]
Huang, Li [1 ,4 ]
Shi, Bing [1 ,5 ]
Yin, Xing [1 ,2 ,6 ]
Zou, Shujuan [1 ,2 ,6 ]
机构
[1] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, Chengdu, Peoples R China
[2] Sichuan Univ, West China Hosp Stomatol, Dept Orthodont, Chengdu, Peoples R China
[3] Sichuan Univ, West China Hosp Stomatol, Dept Jinjiang Clin, Chengdu, Peoples R China
[4] Hosp Chengdu Univ Tradit Chinese Med, Dept stomatol, Chengdu, Peoples R China
[5] Sichuan Univ, West China Hosp Stomatol, Dept Oral & Maxillofacial Surg, Chengdu, Peoples R China
[6] Sichuan Univ, West China Hosp Stomatol, Dept Orthodont, 14,3rd Sect,Ren Min South Rd, Chengdu 610041, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
alpha-ketoglutarate; autophagy; dental implant; osseointegration; osteogenesis; OSTEOBLAST DIFFERENTIATION; MONITORING AUTOPHAGY; MURINE MODEL; BONE-DENSITY; SODIUM-SALT; OSTEOCYTES;
D O I
10.1111/jcpe.13784
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Aim: The osseointegration of dental implants is impaired in patients with osteoporosis, leading to significantly higher failure rates. This study set out to investigate the potential effects of alpha-ketoglutarate (alpha-KG) on implant osseointegration in an osteoporotic mouse model. Materials and Methods: Female C57BL/6 mice received ovariectomy and bilateral first maxillary molar extraction at the age of 7 weeks. Dental implants were inserted 8 weeks after tooth extraction. In one of the groups, alpha-KG was administered via drinking water throughout the experimental period. Specimens were collected on post-implant days (PIDs) 3, 7, 14, and 21 for micro-CT, histological, and immunohistochemical analyses. At the same time, bone-marrow-derived mesenchymal stem cells (BMMSCs) treated with alpha-KG were interrogated for osteogenic differentiation, autophagic activity, and apoptosis. Results: alpha-KG supplementation in drinking water resulted in enhanced dental implant osseointegration in ovariectomized mice, with up-regulated osteogenic and autophagic activity and down-regulated osteoclast differentiation and cell apoptosis. alpha-KG-treated BMMSCs showed enhanced activity in proliferation, sur-vival, colony formation, and osteogenic differentiation, as well as autophagic activity. Conclusions: Systemic alpha-KG supplementation effectively prevents the failure of den-tal implant osseointegration in mice under an osteoporotic state.
引用
收藏
页码:671 / 683
页数:13
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