title: Mangiferin reduces the inhibition of chondrogenic differentiation by IL-1β in mesenchymal stem cells from subchondral bone and targets multiple aspects of the Smad and SOX9 pathways.
abstract: Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1β-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1β (IL-1β). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y-box (SRY-box) containing gene 9 (SOX9), type 2α1 collagen (Col2α1), cartilage link protein, and aggrecan. In IL-1β-stimulated MSCs, mangiferin significantly reversed the production of TGF-β, BMP-2, BMP-4, SOX9, Col2α1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1β-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2α1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.
authors.affiliation: East-West Bone & Joint Research Institute, Kyung Hee University, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. jehuh2551@hanmail.net.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Huh
authors.affiliation: Department of Acupuncture and Moxibustion, College of Oriental Medicine, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. webs0905@naver.com.
authors.forename: Pil-Seong
authors.initials: PS
authors.lastname: Koh
authors.affiliation: Department of Acupuncture and Moxibustion, Kyung Hee University Hospital at Kangdong, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. sbkacu@khu.ac.kr.
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Seo
authors.affiliation: Department of Acupuncture and Moxibustion, Kyung Hee University Hospital at Kangdong, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. icarus08@hanmail.net.
authors.forename: Yeon-Chul
authors.initials: YC
authors.lastname: Park
authors.affiliation: Department of Acupuncture and Moxibustion, Kyung Hee University Hospital at Kangdong, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. byhacu@khu.ac.kr.
authors.forename: Yong-Hyun
authors.initials: YH
authors.lastname: Baek
authors.affiliation: Department of Acupuncture and Moxibustion, College of Oriental Medicine, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. ljdacu@khumc.or.kr.
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Department of Acupuncture and Moxibustion, Kyung Hee University Hospital at Kangdong, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. dspark49@yahoo.co.kr.
authors.forename: Dong-Suk
authors.initials: DS
authors.lastname: Park
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis / Q000187:drug effects*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D055758:SOX9 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D024043:Collagen Type II; D053583:Interleukin-1beta; D055758:SOX9 Transcription Factor; D051785:Smad Proteins; D044004:Xanthones; C013592:mangiferin