Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis

Objective Iodothyronine deiodinases(DIOs)are important selenoproteins that play a key role in the bone and joint diseases.Osteoarthritis(OA)is the most prevalent joint disease especially in elders.This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis.Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques,mcluding GenCLip 3.0,Database for Annotation,Visualization and Integrated Discovery(DAVID),STRING,Cytoscape,and Network Analyst.The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus(GEO)database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3.Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine;GO analysis showed that DIOs were mainly involved in biological processes,such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling;SULT1A1 was the core node of the PPI network;miRNAs and thyroid hormones had some iterations with DIO1 and DI02;Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients(SMD=0.31,95%CI:0.03,0.59,P=0.03).Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone.And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

Iodothyronine deiodinase gene analysis of the Pacific oyster Crassostrea gigas reveals possible conservation of thyroid hormone feedback regulation mechanism in mollusks

Iodothyronine deiodinase catalyzes the initiation and termination of thyroid hormones(THs) effects, and plays a central role in the regulation of thyroid hormone level in vertebrates. In non-chordate invertebrates, only one deiodinase has been identified in the scallop C hlamys farreri. Here, two deiodinases were cloned in the Pacific oyster C rassostrea gigas( Cg Dx and C g Dy). The characteristic in-frame TGA codons and selenocysteine insertion sequence elements in the oyster deiodinase c DNAs supported the activity of them. Furthermore, seven orthologs of deiodinases were found by a tblastn search in the mollusk Lottia gigantea and the annelid C apitella teleta. A phylogenetic analysis revealed that the deiodinase gene originated from an common ancestor and a clade-specific gene duplication occurred independently during the differentiation of the mollusk, annelid, and vertebrate lineages. The distinct spatiotemporal expression patterns implied functional divergence of the two deiodinases. The expression of C g Dx and Cg Dy was influenced by L-thyroxine T4, and putative thyroid hormone responsive elements were found in their promoters, which suggested that the oyster deiodinases were feedback regulated by TH. Epinephrine stimulated the expression level of C g Dx and Cg Dy, suggesting an interaction effect between different hormones. This study provides the first evidence for the existence of a conserved TH feedback regulation mechanism in mollusks, providing insights into TH evolution.