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LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells

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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-beta receptor (LT beta R), 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/beta-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 LT beta R enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.
Author(s)
고수진김도경노의규민영주서혜진유호민이유진정유경조재철주란정천재경최윤숙허숙경
Issued Date
2021
Type
Article
Keyword
Stem cell therapyMesenchymal stem cellsOsteoporosisOssificationCytokinesPhosphatesCell stainingMAPK singnaling cascades
DOI
10.1371/journal.pone.0247368
URI
https://oak.ulsan.ac.kr/handle/2021.oak/6989
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_plos_journals_2491602070&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,LIGHT%20(TNFSF14)%20enhances%20osteogenesis%20of%20human%20bone%20marrow-derived%20mesenchymal%20stem%20cells&offset=0&pcAvailability=true
Publisher
PLOS ONE
Location
미국
Language
영어
ISSN
1932-6203
Citation Volume
16
Citation Number
2
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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