Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors
Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized...
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description | Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease. |
doi_str_mv | 10.3390/ijms21061967 |
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Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21061967</identifier><identifier>PMID: 32183071</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adipocytes ; Aggregates ; Apoptosis ; Cartilage ; Cartilage (articular) ; Cartilage diseases ; Cell culture ; Cell differentiation ; Cell growth ; Cell surface ; Chemical compounds ; Chondrogenesis ; Collagen ; Dehydrogenases ; Differentiation (biology) ; Ganglioside GM3 ; Gangliosides ; Gene expression ; Glycosaminoglycans ; Glycosphingolipids ; Growth factor receptors ; Growth factors ; Mesenchyme ; Pharmacology ; Phosphorylation ; Progenitor cells ; Signal transduction ; Smad protein ; Stem cells ; Studies ; Synovial membrane ; Toluidine blue ; Transforming growth factor-b</subject><ispartof>International journal of molecular sciences, 2020-03, Vol.21 (6), p.1967</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-63c9da762300908f9bfb0a1978c95f47b1a3af4c644cc4f5fb8340faa42ee683</citedby><cites>FETCH-LOGICAL-c478t-63c9da762300908f9bfb0a1978c95f47b1a3af4c644cc4f5fb8340faa42ee683</cites><orcidid>0000-0002-7823-9295</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139639/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139639/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32183071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ryu, Jae-Sung</creatorcontrib><creatorcontrib>Seo, Sang Young</creatorcontrib><creatorcontrib>Jeong, Eun-Jeong</creatorcontrib><creatorcontrib>Kim, Jong-Yeup</creatorcontrib><creatorcontrib>Koh, Yong-Gon</creatorcontrib><creatorcontrib>Kim, Yong Il</creatorcontrib><creatorcontrib>Choo, Young-Kug</creatorcontrib><title>Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.</description><subject>Adipocytes</subject><subject>Aggregates</subject><subject>Apoptosis</subject><subject>Cartilage</subject><subject>Cartilage (articular)</subject><subject>Cartilage diseases</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cell growth</subject><subject>Cell surface</subject><subject>Chemical compounds</subject><subject>Chondrogenesis</subject><subject>Collagen</subject><subject>Dehydrogenases</subject><subject>Differentiation (biology)</subject><subject>Ganglioside GM3</subject><subject>Gangliosides</subject><subject>Gene expression</subject><subject>Glycosaminoglycans</subject><subject>Glycosphingolipids</subject><subject>Growth factor receptors</subject><subject>Growth factors</subject><subject>Mesenchyme</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Progenitor cells</subject><subject>Signal transduction</subject><subject>Smad protein</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Synovial membrane</subject><subject>Toluidine blue</subject><subject>Transforming growth factor-b</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtLAzEUhYMoPqo71xJw48LRvDpJNoJUrYIiSF1KyKRJmzKT1GRG8d87Pqmu7oH7cTj3HgD2MTqhVKJTv2gywajEsuRrYBszQgqESr6-orfATs4LhAglQ7kJtijBgiKOt8HTWIdZ7WP2UwvHdxQ-LosHO-tq3Vo4mscwTXFmgzfwwjtnkw2t162PAVZvcJJ0yC6mBo5TfG3n8EqbNib4YI1d9iLvgg2n62z3vucATK4uJ6Pr4vZ-fDM6vy0M46ItSmrkVPOSUIQkEk5WrkIaSy6MHDrGK6ypdsyUjBnD3NBVgjLktGbE2lLQATj7sl12VWOnpg-ZdK2WyTc6vamovfq7CX6uZvFFcUxlSWVvcPRtkOJzZ3OrGp-NrWsdbOyyIpQLIfnH1wbg8B-6iF0K_XWfFENYCNxTx1-USTHnZN1vGIzUR21qtbYeP1g94Bf-6Ym-A1pzlLU</recordid><startdate>20200313</startdate><enddate>20200313</enddate><creator>Ryu, Jae-Sung</creator><creator>Seo, Sang Young</creator><creator>Jeong, Eun-Jeong</creator><creator>Kim, Jong-Yeup</creator><creator>Koh, Yong-Gon</creator><creator>Kim, Yong Il</creator><creator>Choo, Young-Kug</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7823-9295</orcidid></search><sort><creationdate>20200313</creationdate><title>Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors</title><author>Ryu, Jae-Sung ; 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Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32183071</pmid><doi>10.3390/ijms21061967</doi><orcidid>https://orcid.org/0000-0002-7823-9295</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adipocytes Aggregates Apoptosis Cartilage Cartilage (articular) Cartilage diseases Cell culture Cell differentiation Cell growth Cell surface Chemical compounds Chondrogenesis Collagen Dehydrogenases Differentiation (biology) Ganglioside GM3 Gangliosides Gene expression Glycosaminoglycans Glycosphingolipids Growth factor receptors Growth factors Mesenchyme Pharmacology Phosphorylation Progenitor cells Signal transduction Smad protein Stem cells Studies Synovial membrane Toluidine blue Transforming growth factor-b |
title | Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors |
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