Overexpression Of Aldh6a1 Rescues Osteoblasts And Facilitates Osseointegration In Hyperlipidemia

Endogenous therapeutic targets for facilitating titanium implant osseointegration in hyperlipidemia remain elusive and this study aimed to elucidate the potential role of ALDH6A1 in osseointegration in hyperlipidemia mice. The animal experimental procedures were approved by the Medical Ethics Committee of Stomatological Hospital, Shandong University, Jinan, China. Twenty-four 6-week-old male C57BL/6J mice were used to construct normal or hyperlipidemia femoral implant model, and overexpression of ALDH6A1 was achieved through local injection of lentivirus. Micro-CT and immunofluorescence staining were applied to detect osseointegration, oxidative damage, expression levels of ALDH6A1 in peri-implant tissue. In addition, primary osteoblasts from mouse skull were extracted and cultured for exploring the impact of changes in ALDH6A1 expression levels on the biological activity of osteoblasts. All data were presented as the mean ± standard deviation of at least three independent experiments. The P value less than 0.05 was considered to be statistically significant. In vivo, ALDH6A1 expression significantly decreased in hyperlipidemia mice, compared with normal mice (P < 0.05), and local overexpression of ALDH6A1 facilitated osseointegration in hyperlipidemia mice by reducing oxidative damage in peri-implant tissue. In vitro, ALDH6A1 was downregulated in high-fat environment and silencing ALDH6A1 led to osteogenic dysfunction. Additionally, ALDH6A1 overexpression reduced the fluorescence intensity of DCFH-DA and MitoSOX, and restored the expression of COLI, ALP, and RUNX2. Overexpression of ALDH6A1 significantly reshapes the biological activity of osteoblasts and improves osseointegration under hyperlipidemia. ALDH6A1 is a potential therapeutic target for hyperlipidemia related bone metabolism diseases.