o the wingless-related integration site (WNT) signaling pathways are group of conserved signal transduction pathways made of proteins that regulate a wide range of biological processes including cellular proliferation, embryogenesis, tissue homeostasis, and other systemic effects. It has been recently discovered that any aberration or dysregulation of the Wnt/β-catenin cascade could contribute to the development and progression of variety of disorders and cancers due to its involvement in many physiological processes such as cell proliferation, differentiation, migration, apoptosis, and tissue homeostasis. The canonical Wnt pathway is hyperactivated in SLE and plays a significant role in lupus nephritis pathogenesis and induction of renal fibrosis. Over activation or dysregulation of Wnt signaling may result in an imbalance of bone remodeling in the form of stimulation of bone formation by inducing ostoblastic differentiation, increasing osteoblast proliferation, and inhibiting osteoblast apoptosis. o When Wnt/β-catenin pathway is activated, β-catenin is accumulated and translocated to the nucleus where it forms a transcription activation complex with TCF/LEF that activates the expression of a set of target genes such as fibronectin, fibroblast-specific protein1 (Fsp1), matrix metalloproteinase-7 (MMP7), plasminogeng activator inhibitor-1, Snail-1, and Twist. o It has been suggested that blocking the WNT/β-catenin signaling attenuated renal fibrotic lesions as the overexpression of Dkk-1 inhibited the activation of β-catenin, fibroblast-specific protein 1 and αSMA protein, which inhibited the transformation of myofibroblasts and the synthesis of type I collagen, as well as fibronectin, thus reducing collagen deposition.