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Articular Cartilage Development
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
Wingless and int-Related Proteins: Originally, the wingless genes were identified in Drosophila wing development pathways. Nusse et al. (1984) first described the int family of genes in virus-induced mammary tumors. The int genes were homologous to Drosophila wingless genes, and the nomenclature Wnts derives from the fusion of Wingless and ints. There are about 20 Wnt genes in mammals. Wnts signal via the Frizzled family of cell surface receptors. In the absence of the Wnt ligand, the enzyme glycogen synthase kinase 3 (GSK3) phosphorylates β-catenin and targets it for degradation by proteosomes. However, when Wnt activates the cognate cell surface Frizzled receptors, the GSK3 activity is blocked, rendering the β-catenin stable and resulting in translocation into the nucleus to activate the transcription factor lymphoid enhancer factor (LEF)/T-cell transcription factor (TCF). Wnts have been implicated in articular cartilage homeostasis and function (Nusse 2005).
Benzo[a]pyrene osteotoxicity and the regulatory roles of genetic and epigenetic factors: A review
Published in Critical Reviews in Environmental Science and Technology, 2022
Jiezhang Mo, Doris Wai-Ting Au, Jiahua Guo, Christoph Winkler, Richard Yuen-Chong Kong, Frauke Seemann
MiRNAs serve important roles in regulating cell fate commitment, proliferation, differentiation, maturation and survival/apoptosis of OBs (Figure 5, Table S6). The downregulation of miR-29a inhibits Wnt/β-catenin signaling by upregulating the inhibitors Dickkopf Wnt signaling pathway inhibitor 1 (DKK1), Secreted frizzled-related protein 2 (SFRP2), and Kremen protein 2 (Kremen2), thereby inhibiting osteogenesis (Kapinas et al., 2010), while miR-206 suppresses OB viability by reducing connexin 43 expression (Inose et al., 2009). MiR-182 inhibits OB proliferation and differentiation by suppressing forkhead box protein O1 (FOXO1) expression (Teixeira et al., 2010). MiR-133 and miR-3077-5p inhibit OB differentiation by targeting RUNX2 mRNAs (Liao et al., 2013). MiR-2861 and miR-196a upregulate RUNX2 by targeting histone deacetylase 5 (HDAC5) and homeobox C8 (HOXC8) (Bmp/Smad signaling) (Kim et al., 2009; Li et al., 2009). Additionally, miR-31, miR-93, miR-143, miR-145, miR-214, and miR-637 downregulate OSX expression and inhibit the differentiation of POBs to MOBs, and the activity of MOBs (such as mineralization) (Baglìo et al., 2013; Jia et al., 2013; Li et al., 2014; Shi et al., 2013; Zhang et al., 2011). MiR-214 inhibits bone formation and homeostasis by targeting the mRNA of ATF4 (Wang, Guo, et al., 2013).