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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.

Huh JE, Koh PS, Seo BK, Park YC, Baek YH, Lee JD, Park DS - Int J Mol Sci (2014)

Bottom Line: Mangiferin is a natural immunomodulator found in plants including mango trees.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).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.

View Article: PubMed Central - PubMed

Affiliation: East-West Bone & Joint Research Institute, Kyung Hee University, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. jehuh2551@hanmail.net.

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.

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Histological analysis of mesenchymal stem cells from rabbit subchondral bone undergoing chondrogenic, adipogenic, and osteogenic differentiation. (A) control; (B) chondrogenic differentiation visualized by staining with alcian blue; (C) adipogenic differentiation visualized by staining with Oil Red O; and (D) osteogenic differentiation visualized by staining with Alizarin Red.
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ijms-15-16025-f001: Histological analysis of mesenchymal stem cells from rabbit subchondral bone undergoing chondrogenic, adipogenic, and osteogenic differentiation. (A) control; (B) chondrogenic differentiation visualized by staining with alcian blue; (C) adipogenic differentiation visualized by staining with Oil Red O; and (D) osteogenic differentiation visualized by staining with Alizarin Red.

Mentions: To evaluate the chondrogenic differentiation potential of MSCs from rabbit subchondral bone, cells were cultured for up to 14 days in pellet cultures under standard chondrogenic conditions. Histological analysis using the alcian blue stain showed that progenitor cells developed into a dense tissue, rich in viable cells and proteoglycan (Figure 1B). Adipogenic differentiated cells were visualized through the staining of lipid vacuoles by Oil Red O, and osteogenic cells were detected via the staining of mineralized matrix components with Alizarin red (Figure 1C,D). This study indicates that MSCs from the subchondral bone have a prominent chondrogenic, adipogenic, and osteogenic differentiation potential. In our previous study, MSCs from rabbit subchondral bone showed typical surface antigens, approximately 91%–98% of which were for CD105, CD73, and CD90. In addition to the pluripotency factors OCT4 and NANOG similary express, as do the adult bone marrow-derived MSCs that we examined. Cells were negative for the hematopoietic antigens CD3 and CD34, as well as for the common leukocyte antigen CD45 and the macrophage antigen CD11b [9,10]. In line with the previous studies, these data suggest that MSCs of subchondral bone are similar to MSCs from many other tissues and have potential as a substitute route for cartilage repair.


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.

Huh JE, Koh PS, Seo BK, Park YC, Baek YH, Lee JD, Park DS - Int J Mol Sci (2014)

Histological analysis of mesenchymal stem cells from rabbit subchondral bone undergoing chondrogenic, adipogenic, and osteogenic differentiation. (A) control; (B) chondrogenic differentiation visualized by staining with alcian blue; (C) adipogenic differentiation visualized by staining with Oil Red O; and (D) osteogenic differentiation visualized by staining with Alizarin Red.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4200868&req=5

ijms-15-16025-f001: Histological analysis of mesenchymal stem cells from rabbit subchondral bone undergoing chondrogenic, adipogenic, and osteogenic differentiation. (A) control; (B) chondrogenic differentiation visualized by staining with alcian blue; (C) adipogenic differentiation visualized by staining with Oil Red O; and (D) osteogenic differentiation visualized by staining with Alizarin Red.
Mentions: To evaluate the chondrogenic differentiation potential of MSCs from rabbit subchondral bone, cells were cultured for up to 14 days in pellet cultures under standard chondrogenic conditions. Histological analysis using the alcian blue stain showed that progenitor cells developed into a dense tissue, rich in viable cells and proteoglycan (Figure 1B). Adipogenic differentiated cells were visualized through the staining of lipid vacuoles by Oil Red O, and osteogenic cells were detected via the staining of mineralized matrix components with Alizarin red (Figure 1C,D). This study indicates that MSCs from the subchondral bone have a prominent chondrogenic, adipogenic, and osteogenic differentiation potential. In our previous study, MSCs from rabbit subchondral bone showed typical surface antigens, approximately 91%–98% of which were for CD105, CD73, and CD90. In addition to the pluripotency factors OCT4 and NANOG similary express, as do the adult bone marrow-derived MSCs that we examined. Cells were negative for the hematopoietic antigens CD3 and CD34, as well as for the common leukocyte antigen CD45 and the macrophage antigen CD11b [9,10]. In line with the previous studies, these data suggest that MSCs of subchondral bone are similar to MSCs from many other tissues and have potential as a substitute route for cartilage repair.

Bottom Line: Mangiferin is a natural immunomodulator found in plants including mango trees.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).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.

View Article: PubMed Central - PubMed

Affiliation: East-West Bone & Joint Research Institute, Kyung Hee University, 149, Sangil-dong, Gangdong-gu, Seoul 134-727, Korea. jehuh2551@hanmail.net.

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.

Show MeSH
Related in: MedlinePlus