title: Indirubin-3'-oxime, an activator of Wnt/β-catenin signaling, enhances osteogenic commitment of ST2 cells and restores bone loss in high-fat diet-induced obese male mice.
abstract: Obesity is a growing issue of the modern world, and its negative impact on bones in obese male patients has been recently reported. The Wnt/β-catenin pathway has an established role in the regulation of body fat content and bone density. We investigated the effects of indirubin-3'-oxime (I3O), the GSK3β inhibitor that activates Wnt/β-catenin signaling, on trabecular bone in high-fat diet (HFD)-induced obese male mice. I3O reverses the downregulating effect of fatty acid (FA) on Wnt/β-catenin signaling and enhances the osteogenic commitment of the bone marrow-derived stromal cell line ST2. FA induces the adipogenic differentiation of bone marrow stromal cells in vitro. In a male mouse model of HFD-induced obesity, trabecular bone loss was observed in the femora, with a gross increase in abdominal fat; however, the HFD effects were rescued with the activation of Wnt/β-catenin signaling by I3O treatment. I3O administration also reversed the increase in the number of HFD-induced adipocytes in the femur bone marrow in trabecular bone. Overall, our results indicate that I3O could be a potential therapeutic agent for obese male patients through downregulation of abdominal fat and net increment in trabecular bone density.
authors.affiliation: Translational Research Center for Protein Function Control, Yonsei University, Seoul, South Korea; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zahoor
authors.affiliation: Translational Research Center for Protein Function Control, Yonsei University, Seoul, South Korea; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
authors.forename: Pu-Hyeon
authors.initials: PH
authors.lastname: Cha
authors.affiliation: Translational Research Center for Protein Function Control, Yonsei University, Seoul, South Korea; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea. Electronic address: kychoi@yonsei.ac.kr.
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat; D015870:Gene Expression; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D010091:Oximes / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D007211:Indoles; D010091:Oximes; D051176:beta Catenin; C474021:indirubin-3'-monoxime
keywords: Abdominal fat; Bone loss; GSK3β inhibitor; Indirubin-3′-oxime; Obesity; Wnt/β-catenin