LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells
Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adver...
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| creator | Heo, Sook-Kyoung Choi, Yunsuk Jeong, Yoo Kyung Ju, Lan Jeong Yu, Ho-Min Kim, Do Kyoung Seo, Hye Jin Lee, Yoo Jin Cheon, Jaekyung Koh, SuJin Min, Young Joo Noh, Eui-Kyu Jo, Jae-Cheol |
| description | Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-β receptor (LTβR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy. |
| doi_str_mv | 10.1371/journal.pone.0247368 |
| format | Article |
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Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-β receptor (LTβR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0247368</identifier><identifier>PMID: 33606781</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antibodies ; Biological properties ; Biology and Life Sciences ; Biomedical materials ; Biomedical research ; Bioreactors ; Bone marrow ; Bones ; Cancer ; Cartilage ; Cell differentiation ; Consent ; Cytokines ; Fractures ; Growth ; Growth factors ; Health aspects ; Hematology ; Hospitals ; Immune system ; Medical schools ; Medicine ; Medicine and Health Sciences ; Mesenchymal stem cells ; Microenvironments ; Oncology ; Osteogenesis ; Osteoporosis ; Regeneration (physiology) ; Regenerative medicine ; Research and Analysis Methods ; Stem cells ; Tissue engineering ; Tissues ; Transcription factors ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2021-02, Vol.16 (2), p.e0247368-e0247368</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Heo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Heo et al 2021 Heo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-5e1248623369ea664822d1366847b1fd156c6aca0b37ad947700c9e484ccb0d73</citedby><cites>FETCH-LOGICAL-c659t-5e1248623369ea664822d1366847b1fd156c6aca0b37ad947700c9e484ccb0d73</cites><orcidid>0000-0001-6014-7977</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/PMC7895395/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895395/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33606781$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Papaccio, Gianpaolo</contributor><creatorcontrib>Heo, Sook-Kyoung</creatorcontrib><creatorcontrib>Choi, Yunsuk</creatorcontrib><creatorcontrib>Jeong, Yoo Kyung</creatorcontrib><creatorcontrib>Ju, Lan Jeong</creatorcontrib><creatorcontrib>Yu, Ho-Min</creatorcontrib><creatorcontrib>Kim, Do Kyoung</creatorcontrib><creatorcontrib>Seo, Hye Jin</creatorcontrib><creatorcontrib>Lee, Yoo Jin</creatorcontrib><creatorcontrib>Cheon, Jaekyung</creatorcontrib><creatorcontrib>Koh, SuJin</creatorcontrib><creatorcontrib>Min, Young Joo</creatorcontrib><creatorcontrib>Noh, Eui-Kyu</creatorcontrib><creatorcontrib>Jo, Jae-Cheol</creatorcontrib><title>LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. 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We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.</description><subject>Antibodies</subject><subject>Biological properties</subject><subject>Biology and Life Sciences</subject><subject>Biomedical materials</subject><subject>Biomedical research</subject><subject>Bioreactors</subject><subject>Bone marrow</subject><subject>Bones</subject><subject>Cancer</subject><subject>Cartilage</subject><subject>Cell differentiation</subject><subject>Consent</subject><subject>Cytokines</subject><subject>Fractures</subject><subject>Growth</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Immune system</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mesenchymal stem 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differentiation</topic><topic>Consent</topic><topic>Cytokines</topic><topic>Fractures</topic><topic>Growth</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Immune system</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mesenchymal stem cells</topic><topic>Microenvironments</topic><topic>Oncology</topic><topic>Osteogenesis</topic><topic>Osteoporosis</topic><topic>Regeneration (physiology)</topic><topic>Regenerative medicine</topic><topic>Research and Analysis Methods</topic><topic>Stem cells</topic><topic>Tissue engineering</topic><topic>Tissues</topic><topic>Transcription factors</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heo, Sook-Kyoung</creatorcontrib><creatorcontrib>Choi, Yunsuk</creatorcontrib><creatorcontrib>Jeong, Yoo Kyung</creatorcontrib><creatorcontrib>Ju, 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Yoo Kyung</au><au>Ju, Lan Jeong</au><au>Yu, Ho-Min</au><au>Kim, Do Kyoung</au><au>Seo, Hye Jin</au><au>Lee, Yoo Jin</au><au>Cheon, Jaekyung</au><au>Koh, SuJin</au><au>Min, Young Joo</au><au>Noh, Eui-Kyu</au><au>Jo, Jae-Cheol</au><au>Papaccio, Gianpaolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-02-19</date><risdate>2021</risdate><volume>16</volume><issue>2</issue><spage>e0247368</spage><epage>e0247368</epage><pages>e0247368-e0247368</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-β receptor (LTβR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33606781</pmid><doi>10.1371/journal.pone.0247368</doi><orcidid>https://orcid.org/0000-0001-6014-7977</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2021-02, Vol.16 (2), p.e0247368-e0247368 |
| issn | 1932-6203 1932-6203 |
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| source | PubMed Central Free; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Antibodies Biological properties Biology and Life Sciences Biomedical materials Biomedical research Bioreactors Bone marrow Bones Cancer Cartilage Cell differentiation Consent Cytokines Fractures Growth Growth factors Health aspects Hematology Hospitals Immune system Medical schools Medicine Medicine and Health Sciences Mesenchymal stem cells Microenvironments Oncology Osteogenesis Osteoporosis Regeneration (physiology) Regenerative medicine Research and Analysis Methods Stem cells Tissue engineering Tissues Transcription factors Tumor necrosis factor-TNF |
| title | LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T09%3A03%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=LIGHT%20(TNFSF14)%20enhances%20osteogenesis%20of%20human%20bone%20marrow-derived%20mesenchymal%20stem%20cells&rft.jtitle=PloS%20one&rft.au=Heo,%20Sook-Kyoung&rft.date=2021-02-19&rft.volume=16&rft.issue=2&rft.spage=e0247368&rft.epage=e0247368&rft.pages=e0247368-e0247368&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0247368&rft_dat=%3Cgale_plos_%3EA652346026%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2491602070&rft_id=info:pmid/33606781&rft_galeid=A652346026&rft_doaj_id=oai_doaj_org_article_f2456040129c4785a64b155bb87dedd3&rfr_iscdi=true |