Dysregulated expression of genes involved in ER stress and chondrocyte differentiation.
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(A) Immunofluorescent analysis for ATF4 in tibial epiphyseal cryosections from 2 week wildtype (Wt), Xbp1CartΔEx2, ColXN617K and C/X mice; B—Bone; HZ—Hypertrophic Zone; PZ—Proliferative Zone. (B-H) qPCR with primers specific for (B) Chop, (C) Cebpb, (D) p57Kip2, (E) Gadd45b, (F) Runx2, (G) Col10a1, and (H) Mmp13 on cDNA derived from Wt, Xbp1CartΔEx2, ColXN617K and C/X hypertrophic zone aRNA. Plots depict mean fold differences with standard deviation from the mean; N = 3; statistical analysis performed using Student’s t test, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. (I) Schematic diagram of proposed model to explain the molecular pathology of MCDS. Blue boxes depict genes. Red boxes depict biological processes. Green arrows depict activation or up-regulation. Red arrows depict inactivation or down-regulation. Green lines depict increased interaction between proteins. Red lines depict decreased interaction between proteins.