title: Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality.
abstract: Omega-3 fatty acids (FAs) are essential nutritional components that must be obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial for bone health, and several mechanisms have been suggested to mediate their effects on bone, including alterations in calcium absorption and urinary calcium loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and inhibition of osteoclastogenesis. However, to date, there is scant information regarding the effect of omega-3 FAs on the developing skeleton during the rapid growth phase. In this study we aim to evaluate the effect of exposure to high levels of omega-3 FAs on bone development and quality during prenatal and early postnatal period. For this purpose, we used the fat-1 transgenic mice that have the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic cell line as models. We show that exposure to high concentrations of omega-3 FAs at a young age accelerates bone growth through alterations of the growth plate, associated with increased chondrocyte proliferation and differentiation. We further propose that those effects are mediated by the receptors G-protein coupled receptor 120 (GPR120) and hepatic nuclear factor 4α, which are expressed by chondrocytes in culture. Additionally, using a combined study on the structural and mechanical bone parameters, we show that high omega-3 levels contribute to superior trabecular and cortical structure, as well as to stiffer bones and improved bone quality. Most interestingly, the fat-1 model allowed us to demonstrate the role of maternal high omega-3 concentration on bone growth during the gestation and postnatal period.
authors.affiliation: Institute of Biochemistry and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Netta
authors.initials: N
authors.lastname: Koren
authors.affiliation: Institute of Biochemistry and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Stav
authors.initials: S
authors.lastname: Simsa-Maziel
authors.affiliation: Koret School of Veterinary, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Shahar
authors.affiliation: Institute of Biochemistry and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Betty
authors.initials: B
authors.lastname: Schwartz
authors.affiliation: Institute of Biochemistry and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel. Electronic address: efrat.mo@mail.huji.ac.il.
authors.forename: Efrat
authors.initials: E
authors.lastname: Monsonego-Ornan
mesh_terms: D000818:Animals; D015519:Bone Density; D001846:Bone Development; D001848:Bone Diseases, Developmental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis* / Q000627:therapeutic use; D005260:Female; D051557:Hepatocyte Nuclear Factor 4 / Q000819:agonists / Q000378:metabolism; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010012:Osteogenesis; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D012727:Sex Characteristics; D013047:Specific Pathogen-Free Organisms
chemical_list: D029742:Caenorhabditis elegans Proteins; C498007:FFAR4 protein, mouse; D015525:Fatty Acids, Omega-3; D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D043562:Receptors, G-Protein-Coupled; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases
keywords: Bone mechanics; Bone structure; Chondrocyte differentiation; Growth plate; ω-3 Desaturase; ω-3 Fatty acids