title: Zinc finger protein 467 regulates Wnt signaling by modulating the expression of sclerostin in adipose derived stem cells.
abstract: Osteoporosis is a metabolic disease in which a disruption of the balance between bone formation by osteoblasts and bone resorption by osteoclasts leads to the progressive deterioration of bone density and quality. Tissue engineering approaches to the treatment of osteoporosis depend on the identification of factors that promote the differentiation of progenitor cells towards an osteoblastic phenotype. In the present study, we expanded on prior findings on the role of zinc finger protein 467 (Zfp467) in the osteoblastic differentiation of adipose-derived stem cells (ADSCs) and explored the underlying mechanisms. We showed that Zfp467 binds to and regulates the expression of the SOST gene, which encodes a secreted glycoprotein named sclerostin (Sost) that is expressed exclusively by osteocytes and functions as a negative regulator of bone formation through the modulation of Wnt signaling. Overexpression of Zfp467 in ADSCs inhibited Wnt signaling by promoting binding of Sost to the Wnt coreceptors LRP5/6 and disrupting Wnt induced Frizzled-LRP6 complex formation, and siRNA mediated Sost silencing reversed the inhibition of Wnt signaling by Zfp467 in ADSCs. Our results indicate that Zfp467 regulates the differentiation of ADSCs via a mechanism involving Sost-mediated inhibition of Wnt signaling, suggesting potential therapeutic targets for the treatment of osteoporosis.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: youlisky2002@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: You
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Wen-Sha
authors.initials: WS
authors.lastname: Gu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse; D051153:Wnt Proteins; C572221:zinc finger protein 467, mouse
keywords: ADSCs; Sost; Wnt signaling; Zfp467