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

J Clin Periodontol

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Published: May 2023

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 (α-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, 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.

Results: 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.

Conclusions: Systemic α-KG supplementation effectively prevents the failure of dental implant osseointegration in mice under an osteoporotic state.

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Source
http://dx.doi.org/10.1111/jcpe.13784DOI Listing

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