Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice

• Published in: PloS one 2016-07, Vol.11 (7), p.e0159375-e0159375
• Main Authors: Kikuchi, Manami, Shimada, Masako, Matsuzaka, Takashi, Ishii, Kiyoaki, Nakagawa, Yoshimi, Takayanagi, Misa, Yamada, Nobuhiro, Shimano, Hitoshi
• Format: Article
• Language: English
• Subjects: Acetyltransferases - genetics; Acetyltransferases - physiology; Animals; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Biosynthesis; Cancellous bone; Cartilage cells; Cell differentiation; Cell Differentiation - physiology; Cell proliferation; Cell Proliferation - physiology; Chondrocytes; Chondrocytes - cytology; Chondrocytes - metabolism; Chondrogenesis; Collagen; Diabetes; Differentiation; Elongation; Embryogenesis; Embryonic development; Embryos; Endocrinology; Experiments; Families & family life; Fatty acids; Gene expression; Growth plate; Growth Plate - growth & development; Insulin; Insulin resistance; Internal medicine; Lipids; Medicine; Medicine and Health Sciences; Metabolic syndrome; Mice; Mice, Knockout; Osteoblasts - metabolism; Phosphatase; Rodents; Skeleton; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159375

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.