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.
Highlights
Metabolic syndrome is a combination of the medical disorders including obesity, hyperglycemia, insulin resistance, and dyslipidemia, and increases the risk for diabetes and cardiovascular diseases
Chondrocyte, and osteoclast lineages showed 2- to 7-times higher Elovl6 expression than liver (S1B Fig). These results suggest that Elovl6 is ubiquitously expressed in cells of the osteoblast, chondrocyte, and osteoclast lineages and that it could play a physiological role in bone and cartilage in vivo
Ablation of Elovl6 exhibited reduced proliferating and elongated hypertrophic chondrocyte layers in growth plate and reduced trabecular bone with the increased number of osteoclast-like cells in the primary spongiosa of the proximal tibia. This bone phenotype was suggestive of an importance of Elovl6 in cells of the chondrocyte, osteoblast, and osteoclast lineages
Summary
Metabolic syndrome is a combination of the medical disorders including obesity, hyperglycemia, insulin resistance, and dyslipidemia, and increases the risk for diabetes and cardiovascular diseases. It is estimated, for example, that approximately one thirds of the US population suffers from metabolic syndrome [1, 2]. Elovl knockout mice showed a marked resistant to diet-induced hyperinsulinemia, atherosclerosis, and steatohepatitis presumably due to the altered fatty acid composition in the liver and macrophages, respectively [5,6,7]. To test our hypothesis and identify a potential link between fatty acids and growth plate development, we performed basal skeletal analysis mainly on hind limb specimens isolated from control and Elovl knockout perinatal mice in this study
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
