title: Epigallocatechin-3-gallate protects against tumor necrosis factor alpha induced inhibition of osteogenesis of mesenchymal stem cells.
abstract: Anabolic bone accruement through osteogenic differentiation is important for the maintenance of physiological bone mass and often disrupted in various inflammatory diseases. Epigallocatechin-3-gallate, as an antioxidant and anti-inflammatory agent, has been suggested for potential therapeutic use in this context, possibly by the inhibition of bone resorption as well as the enhancement of bone formation through directly activating osteoblast differentiation. However, the reported effects of epigallocatechin-3-gallate modulating osteoblast differentiation are mixed, and the underlying molecular mechanism is still elusive. Moreover, there is limited information regarding the effects of epigallocatechin-3-gallate on osteogenic potential of mesenchymal stem cell in inflammation. Here, we examined the in vitro osteogenic differentiation of human mesenchymal stem cells. We found that the cell viability and osteoblast differentiation of human bone marrow-derived mesenchymal stem cells are significantly inhibited by inflammatory cytokine TNFα treatment. Epigallocatechin-3-gallate is able to enhance the cell viability and osteoblast differentiation of mesenchymal stem cells and is capable of reversing the TNFα-induced inhibition. Notably, only low doses of epigallocatechin-3-gallate have such benefits, which potentially act through the inhibition of NF-κB signaling that is stimulated by TNFα. These data altogether clarify the controversy on epigallocatechin-3-gallate promoting osteoblast differentiation and further provide molecular basis for the putative clinical use of epigallocatechin-3-gallate in stem cell-based bone regeneration for inflammatory bone loss diseases, such as rheumatoid arthritis and prosthetic osteolysis.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Xu
authors.affiliation: School of Medicine, Nantong University, Nantong 226019, China The first two authors contributed equally to this work.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, China romly80@sohu.com.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Cui
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate
keywords: EGCG; NF-κB; TNFα; inflammatory bone disease; mesenchymal stem cell; osteoblast differentiation