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

Abstract

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 (α-KG) on implant osseointegration in an osteoporotic mouse model. 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, α-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 α-KG were interrogated for osteogenic differentiation, autophagic activity, and apoptosis. α-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. α-KG-treated BMMSCs showed enhanced activity in proliferation, survival, colony formation, and osteogenic differentiation, as well as autophagic activity. Systemic α-KG supplementation effectively prevents the failure of dental implant osseointegration in mice under an osteoporotic state.