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

PLoS One. 2016 Jul 28;11(7):e0159375. doi: 10.1371/journal.pone.0159375. eCollection 2016.

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.

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / physiology*
  • Animals
  • Cell Differentiation / physiology*
  • Cell Proliferation / physiology*
  • Chondrocytes / cytology*
  • Chondrocytes / metabolism
  • Fatty Acid Elongases
  • Growth Plate / growth & development*
  • Mice
  • Mice, Knockout
  • Osteoblasts / metabolism

Substances

  • Elovl6 protein, mouse
  • Acetyltransferases
  • Fatty Acid Elongases

Grant support

This work is supported by JSPS Kaken Houga #26560393 to MS and AMED-CREST to HS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.