title: Reversine increases the plasticity of lineage-committed preadipocytes to osteogenesis by inhibiting adipogenesis through induction of TGF-β pathway in vitro.
abstract: Reversine has been reported to reverse differentiation of lineage-committed cells to mesenchymal stem cells (MSCs), which then enables them to be differentiated into other various lineages. Both adipocytes and osteoblasts are known to originate from common MSCs, and the balance between adipogenesis and osteogenesis in MSCs is reported to modulate the progression of various human diseases, such as obesity and osteoporosis. However, the role of reversine in modulating the adipogenic potential of lineage-committed preadipocytes and their plasticity to osteogenesis is unclear. Here we report that reversine has an anti-adipogenic function in 3T3-L1 preadipocytes in vitro and alters cell morphology and viability. The transforming growth factor-β (TGF-β) pathway appears to be required for the anti-adipogenic effect of reversine, due to reversine-induced expression of genes involved in TGF-β pathway and reversal of reversine-inhibited adipogenesis by inhibition of TGF-β pathway. We show that treatment with reversine transformed 3T3-L1 preadipocytes into MSC-like cells, as evidenced by the expression of MSCs marker genes. This, in turn, allowed differentiation of lineage-committed 3T3-L1 preadipocytes to osteoblasts under the osteogenic condition in vitro. Collectively, these findings reveal a new function of reversine in reversing lineage-committed preadipocytes to osteogenesis in vitro, and provide new insights into adipose tissue-based regeneration of osteoblasts.
authors.affiliation: Department of Animal Science and Biotechnology, Gyeongnam National University of Science and Technology, 33 Dongjin-ro, Jinju 660-758, Republic of Korea.
authors.forename: Jeong Geun
authors.initials: JG
authors.lastname: Park
authors.affiliation: Sempio Fermentation Research Center, Sempio Foods Company, 183 Osongsaengmyeong 4ro, Osongeup, Cheongwongun, Chungcheongbukdo 363-954, Republic of Korea.
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Animal Science and Biotechnology, Gyeongnam National University of Science and Technology, 33 Dongjin-ro, Jinju 660-758, Republic of Korea. Electronic address: ysmoon@gntech.ac.kr.
authors.forename: Yang Soo
authors.initials: YS
authors.lastname: Moon
authors.affiliation: Department of Food Science, Purdue University, West Lafayette, IN 47907, United States. Electronic address: keehong@purdue.edu.
authors.forename: Kee-Hong
authors.initials: KH
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D054337:Cell Dedifferentiation / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011687:Purines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D009025:Morpholines; D011687:Purines; D016212:Transforming Growth Factor beta; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine
keywords: 3T3-L1; Adipogenesis; Osteogenesis; Preadipocytes; Reversine; TGF-β