Aberrant Calreticulin expression in articular cartilage of Dio2 deficient mice

Microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice. The beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis.本研究对野生型与Dio2基因敲除（Dio2-/-）小鼠的膝关节软骨组织的微阵列芯片数据（Microarray data，采用Illumina MouseWG-6 v2芯片检测）进行了重新分析，旨在识别不受强制跑台运动（forced treadmill-running）所致机械负荷条件影响的差异表达基因。针对Dio2基因敲除小鼠（N=9）与野生型小鼠（N=11）的关节软骨开展差异表达分析，设定筛选阈值为校正后P值<0.05（错误发现率，FDR）且折叠变化（FC）的绝对值>1.5，最终在钙网蛋白（Calreticulin, Calr）基因位点发现1个探针信号在Dio2基因敲除小鼠中显著下调。Dio2基因敲除小鼠的关节软骨呈现有益的稳态状态，同时伴随钙网蛋白（Calr）的显著低表达。功能分析进一步证实，钙网蛋白（Calr）的表达上调可作为软骨破坏的起始诱因。本研究旨在对比野生型与Dio2基因敲除小鼠的软骨基因表达谱的内在差异，以此作为探究维持组织长期健康稳态的调控因素的研究方法。