期刊
PLOS ONE
卷 16, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0247368
关键词
-
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2018R1D1A1B07051343, NRF-2017R1A1A3A04069314]
- Basic Science Research Program through the Biomedical Research Center - Ulsan University Hospital [UUHBRC-2016-001]
Osteoporosis is a progressive skeletal disease affecting millions worldwide, currently treated with drugs that have severe side effects. Cell replacement therapy using mesenchymal stem cells may be a future treatment strategy. This study found that LIGHT can enhance osteogenesis of hBM-MSCs, possibly through WNT/β-catenin pathway activation.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据