Abstract
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.
Highlights
Osteoblast progenitors have the potential to differentiate into osteoblasts or adipocytes.The commitment and differentiation of osteoblast progenitors towards an adipogenic or osteogenic cell fate depend on a variety of signaling and transcription factors
Van de Vyver et al mentioned that chronic administration of the insulin-sensitising drugs, thiazolidinediones, results in low bone mineral density and fatty bones because mesenchymal stem cells (MSCs) may differentiate towards adipogenesis rather than osteogenesis [3]
Our results suggest that lipids, Chol, DC-Chol and dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP), may stimulate osteoclastogenesis through the inhibition of osteoblast mineralization and the suppression of OPG/RANKL ratio (Figure 3D)
Summary
The commitment and differentiation of osteoblast progenitors towards an adipogenic or osteogenic cell fate depend on a variety of signaling and transcription factors. Increased evidence suggests that an inverse correlation exists between adipogenesis and osteogenesis in mesenchymal stem. Molecules 2018, 23, 95 cells (MSCs) [1]. Previous studies have demonstrated that the disruption of the balance between osteogenesis and adipogenesis could lead to bone diseases such as osteoarthritis (OA) and osteoporosis [2]. Van de Vyver et al mentioned that chronic administration of the insulin-sensitising drugs, thiazolidinediones, results in low bone mineral density and fatty bones because MSC may differentiate towards adipogenesis rather than osteogenesis [3]. Balanced osteoblastic and adipogenic differentiation is critical for the maintenance of healthy bone and lean body composition [4]
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