title: Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway.
abstract: Naringin exhibits antiinflammatory activity and is shown to induce bone formation. Yet the impact of naringin on inflammation-affected bone marrow-derived mesenchymal stem cell (BM-MSC), a promising tool for the regenerative treatment of bone injury, remained to be investigated. We first cultured and characterized the BM-MSCs in vitro and observe the effects of treatments of TNF-α, naringin, or the combination of both on osteogenic differentiation. TNF-α administered at the concentration of 20 ng/ml results in significant reductions in MSC's cell survival, alkaline phosphatase activity and expressions of two osteogenic genes, Runx2 and Osx. Simultaneous treatment of both TNF-α and naringin is able to rescue such reductions. Further mechanistic studies indicate that TNF-α treatment activates the NF-кB signaling pathway, evidenced by elevated p-IкBα level as well as the increased nuclear fraction of NF-кB subunit, p65. Finally, treatment with both TNF-α and naringin decreases expressions of p-IкBα and nuclear p65, and thus represses NF-кB pathway activated by sole TNF-α treatment. Our findings provide a molecular basis by which naringin restores the TNF-α-induced damage in MSCs and provide novel insights into the application of naringin in the MSC-based treatments for inflammation-induced bone injury.
authors.affiliation: Department of Orthopaedics, Hua Dong Hospital Affiliated to Fudan University, Shanghai, 200040, China.
authors.forename: Xvhai
authors.initials: X
authors.lastname: Cao
authors.forename: Weilong
authors.initials: W
authors.lastname: Lin
authors.forename: Chengwei
authors.initials: C
authors.lastname: Liang
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Fengjian
authors.initials: F
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianyong
authors.initials: J
authors.lastname: Feng
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D044950:Flavanones / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D000076182:Sp7 Transcription Factor; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D050659:Core Binding Factor Alpha 1 Subunit; D044950:Flavanones; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; C498144:Rela protein, mouse; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C005274:naringin