Benzofuran pyran compound rescues rat and human osteoblast from lipotoxic effect of palmitate by inhibiting lipid biosynthesis and promoting stabilization of RUNX2. (August 2020)

• Record Type: Journal Article
• Authors: Tripathi, Ashish Kumar; Rai, Divya; Kothari, Priyanka; Kushwaha, Pragati; Sinha, Shradha; Sardar, Anirban; Sashidhara, Koneni V.; Trivedi, Ritu
• Is Part Of: Toxicology in vitro. Volume 66(2020)
• Publication Date: 2020-08
• Subjects: Palmitate -- Osteoblast -- Lipotoxicity -- Apoptosis; Acetyl Co-Carboxylase (ACC) -- Fatty acid synthase (FAS) -- Lactate dehydrogenase (LDH) -- Runt-related transcription factor 2 (RUNX2) -- Osteocalcin (OCN) -- Bone morphogenetic protein 2(BMP2) -- Human osteoblast (HOB); Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.104872
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Obesity and ageing increases bone marrow fat which in turn is associated with lower bone mass. Marrow adipocytes by secreting cytokines, adipokines and free fatty acids change the bone marrow milieu and thus the number of osteoblasts. Palmitate is the common saturated fatty acid, an unavoidable ingredient we consume with food, which kindles cell apoptosis. Compound 4e is osteogenic in nature. We examine the effect of compound 4e in palmitate induced lipotoxicity in rat osteoblasts. Design of benzofuran Pyran hybrid compound (4e) was found to be effective in inhibiting palmitate induced cell apoptosis. In this study an in vitro model of palmitate was contrived. Anti-apoptotic effect of compound 4e was assessed by Annexin/PI and LDH (Lactate dehydrogenase) assay. Compound 4e also increased osteoblast differentiation and mineralization. It also increased expression of osteogenic markers (RUNX2 and BMP2), assessed by Real time PCR and immunofluorescence, which was impeded by palmitate. Acetyl Co-Carboxylase (ACC) and Fatty acid synthase (FAS), two prominent mediators of lipid biosynthesis were increased by palmitate exposure. Compound 4e modulated lipid biosynthesis by inhibiting ACC and FAS as reflected visually and after quantification of less lipid droplet formation suggesting that 4e is osteogenic and simultaneously anti-lipotoxic. Graphical abstract: Unlabelled Image Highlights: Sodium palmitate, a saturated fatty acid, induces cell apoptosis in osteoblast. Compound 4e (Benzofuran pyran compound) ameliorates lipotoxic effect of sodium palmitate and rescue osteoblast. Compound 4e increased expression of osteogenic genes which was downregulated by Palmitate.