Effects of Palovarotene on Ext1-deficient and wild type cultured mouse chondrocytes

Palovarotene, the agonist of the retionic acid nuclear receptor gamma has been shonw to inhibit osteochondroma formation in the mouse osteochondroma models. To understand the biological cation of Palovarotene, the transcriptome analysis was performed using 3D chondrocyte cultures Compaison of Palovarotene-treated groups with vehicle control groups demonstrated the gene lists and biological pathway modulated by Palovarotene-activated retionic acid receptor signaling pathways. The epiphyseal chondrocytes are isolated from proxiimal tibia and deistal femur growth plate from the Ext1-mutant mice (the compound mice of the AggrecanCreER and Ext1e2neofloxed mice) and the control mice (Ext1e2neofloxed mice) at postnatal 10 days of age after tamoxifen injections at postnatal 5 and 7 days of ages. Th isolated cells were embeded in alginate beads and cultured in high glucose DMEM containing 10 % FBS. The cultures were then treated with 300 nM Palovaroten or the same volume of 100% ethanol for 2 days. The cells were collected from the alginate beads and subjected to the bulk RNAseq. There are 4 goups (Aggrecan;Ext1e2nelf/e2neof with vehicel or Palovarotene and Ext1e2neof/2eneof with vehicel or Palovarotene)