Intraperitoneal myriocin upregulates transforming growth factor b1 (tgf‐b1) expression in murine destabilization of the medial meniscus model of osteoarthritis—evidence for a role of ceramide species in cartilage homeostasis

Abstract

Ceramides are biologically active sphingolipids known to play a role in numerous physiological and pathological processes. In particular, ceramides are known mediators in insulin resistance, and are found in increased abundance in osteoarthritic synovial fluid. Given the comorbidity between osteoarthritis and insulin resistance, we hypothesized that ceramides mediate cartilage catabolism in murine models of osteoarthritis. Further, that downregulation of ceramide synthesis would prevent structural damage and normalize biomarkers associated with osteoarthritis ‐ tgf‐b1, HtrA‐1, Ddr‐2, and Mmp‐13. To test this hypothesis, we performed surgical destabilization of the medial meniscus on the right knee of 8‐week‐old mice, treating one group with the serine palmitoyltransferase inhibitor myriocin and the other with a vehicle. An untreated sham group served as the control. We found myriocin administration failed to protect the joint from surgically‐induced cartilage degradation, and that no statistically significant difference occurred in the biomarkers measured with the notable exception of tgf‐b1, which was significantly increased in myriocin‐treated mice. Our findings lead us to the novel conclusion that ceramide species play an important role in cartilage homeostasis, acting specifically through regulating expression of tgf‐b1.Support or Funding InformationBrigham Young University ORCA GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.