Interaction of high lipogenic states with titanium on osteogenesis

• Published in: Bone (New York, N.Y.) N.Y.), 2024-11, Vol.188, p.117242, Article 117242
• Main Authors: Pinto, T.S., van der Eerden, B.C., Schreuders-Koedam, M., van de Peppel, J., Ayada, I., Pan, Q., Verstegen, M.M., van der Laan, L.J., Fuhler, G.M., Zambuzzi, W.F., Peppelenbosch, M.P.
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Bone regeneration; Hepatocytes - metabolism; Humans; Lipogenesis - drug effects; Lipogenic states; Mesenchymal Stem Cells - metabolism; Metabolic disorders; Organoids - metabolism; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteogenesis; Osteogenesis - drug effects; Titanium - pharmacology; Titanium implants
• ISSN: 8756-3282; 1873-2763; 1873-2763
• DOI: 10.1016/j.bone.2024.117242

As obesity rates continue to rise, the prevalence of metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), a new term for Nonalcoholic Fatty Liver Disease (NAFLD), also increases. In an aging population, it is crucial to understand the interplay between metabolic disorders, such as MetALD, and bone health. This understanding becomes particularly significant in the context of implant osseointegration. This study introduces an in vitro model simulating high lipogenesis through the use of human Mesenchymal Stroma Cells-derived adipocytes, 3D intrahepatic cholangiocyte organoids (ICO), and Huh7 hepatocytes, to evaluate the endocrine influence on osteoblasts interacting with titanium. We observed a significant increase in intracellular fat accumulation in all three cell types, along with a corresponding elevation in metabolic gene expression compared to the control groups. Notably, osteoblasts undergoing mineralization in this high-lipogenesis environment also displayed lipid vesicle accumulation. The study further revealed that titanium surfaces modulate osteogenic gene expression and impact cell cycle progression, cell survival, and extracellular matrix remodeling under lipogenic conditions. These findings provide new insights into the challenges of implant integration in patients with obesity and MetALD, offering a deeper understanding of the metabolic influences on bone regeneration and implant success. •nHA titanium increased FAK phosphorylation under high lipogenesis, unlike DAE titanium.•High lipogenesis from Huh7 reduced CDK2 phosphorylation, but nHA titanium prevented it.•nHA titanium maintained the increase in BGLAP expression under high adipogenesis.•The 3D liver organoid model induced more fat droplets in osteoblasts than the 2D model.