title: Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice.
abstract: ELOVL family member 6, elongation of very long chain fatty acids (Elovl6) is a microsomal enzyme, which regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 has been shown to be associated with various pathophysiologies including insulin resistance, atherosclerosis, and non-alcoholic steatohepatitis. To investigate a potential role of Elovl6 during bone development, we here examined a skeletal phenotype of Elovl6 knockout (Elovl6-/-) mice. The Elovl6-/- skeleton was smaller than that of controls, but exhibited no obvious patterning defects. Histological analysis revealed a reduced length of proliferating and an elongated length of hypertrophic chondrocyte layer, and decreased trabecular bone in Elovl6-/- mice compared with controls. These results were presumably due to a modest decrease in chondrocyte proliferation and accelerated differentiation of cells of the chondrocyte lineage. Consistent with the increased length of the hypertrophic chondrocyte layer in Elovl6-/- mice, Collagen10α1 was identified as one of the most affected genes by ablation of Elovl6 in chondrocytes. Furthermore, this elevated expression of Collagen10α1 of Elovl6-null chondrocytes was likely associated with increased levels of Foxa2/a3 and Mef2c mRNA expression. Relative increases in protein levels of nuclear Foxa2 and cytoplasmic histone deacethylase 4/5/7 were also observed in Elovl6 knockdown cells of the chondrocyte lineage. Collectively, our data suggest that Elovl6 plays a critical role for proper development of embryonic growth plate.
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.|Graduate School of Nutritional Science, Sagami Women's University, Kanagawa, Japan.
authors.forename: Masako
authors.identifier: http://orcid.org/0000-0002-8384-780X
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaka
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.|International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Nutritional Science, Sagami Women's University, Kanagawa, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Takayanagi
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.|International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan.|AMED-CREST, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D000081031:Fatty Acid Elongases; D006132:Growth Plate / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism
chemical_list: C000630968:Elovl6 protein, mouse; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases