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The Impact of Lipid Types and Liposomal Formulations on Osteoblast Adiposity and Mineralization

Department of Medical Research and Development, Chang Gung Memorial Hospital Chiayi Branch, Chiayi 61363, Taiwan
Department of Orthopaedics, Chiayi Branch, Taichung Veterans General Hospital, No. 600, Sec. 2, Shixian Road, West District, Chiayi City 60090, Taiwan
Department of Biochemical Science and Technology, National Chia Yi University, No. 300, Syuefu Rd, Chiayi City 60004, Taiwan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2018, 23(1), 95;
Received: 4 December 2017 / Revised: 22 December 2017 / Accepted: 29 December 2017 / Published: 2 January 2018
(This article belongs to the Special Issue Liposomes as Drug Carriers)
PDF [3336 KB, uploaded 23 January 2018]


Recent studies have demonstrated that fat accumulation in bone cells is detrimental to bone mass. Both adipocytes and osteoblasts are derived from common multipotent mesenchymal stem cells (MSCs) and hence the presence of fat may increase adipocyte proliferation, differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Lipids are common constituents in supramolecular vesicles (e.g., micelles or liposomes) that serve as drug delivery systems. Liposomal formulations such as Meriva® were proven to decrease joint pain and improve joint function in osteoarthritis (OA) patients. In this study, we evaluated how lipid types and liposomal formulations affect osteoblast behavior including cell viability, differentiation, mineralization and inflammation. Various liposomal formulations were prepared using different types of lipids, including phosphatidylcholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE), cholesterol (Chol), 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol HCl), and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) to investigate the impact on osteoblast differentiation and inflammation. The results indicated that cationic lipids, DC-cholesterol and DOTAP, presented higher dose-dependent cytotoxicity and caused high level of inflammatory responses. Due to the natural properties of lipids, all the lipids can induce lipid droplet formation in osteoblasts but the level of lipid droplet accumulation was different. In comparison with cationic lipids, neutral lipids induced less adiposity, and maintained high osteoblast mineralization. Similar to previous researches, we also confirmed an inverse relationship between lipid droplet formation and osteoblast mineralization in 7F2 mouse osteoblasts. Importantly, PC containing liposomes (PC only and PC/DOTAP) suppressed IL-1β-induced gene expression of COX-2 and MMP-3 but not Chol/DOTAP liposomes or DC-Chol/DOPE liposomes. Taken together, we suggested that PC contained liposomes could provide the best liposomal formulation for the treatment of bone diseases. View Full-Text
Keywords: lipid; liposomal formulation; osteogenesis; lipid droplet accumulation; osteoblast lipid; liposomal formulation; osteogenesis; lipid droplet accumulation; osteoblast

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Chang, S.-F.; Yeh, C.-C.; Chen, P.-J.; Chang, H.-I. The Impact of Lipid Types and Liposomal Formulations on Osteoblast Adiposity and Mineralization. Molecules 2018, 23, 95.

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