A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis.
Development of adipose tissue requires the differentiation of less specialized cells, such as human mesenchymal stem cells (hMSCs), into adipocytes. Since matrix metalloproteinases (MMPs) play critical roles in the cell differentiation process, we conducted investigations to determine if a novel mer...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5325569?pdf=render |
| _version_ | 1818214190280605696 |
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| author | Dale B Bosco Mark D Roycik Yonghao Jin Martin A Schwartz Ty J Lively Diego A R Zorio Qing-Xiang Amy Sang |
| author_facet | Dale B Bosco Mark D Roycik Yonghao Jin Martin A Schwartz Ty J Lively Diego A R Zorio Qing-Xiang Amy Sang |
| author_sort | Dale B Bosco |
| collection | DOAJ |
| description | Development of adipose tissue requires the differentiation of less specialized cells, such as human mesenchymal stem cells (hMSCs), into adipocytes. Since matrix metalloproteinases (MMPs) play critical roles in the cell differentiation process, we conducted investigations to determine if a novel mercaptosulfonamide-based MMP inhibitor (MMPI), YHJ-7-52, could affect hMSC adipogenic differentiation and lipid accumulation. Enzyme inhibition assays, adipogenic differentiation experiments, and quantitative PCR methods were employed to characterize this inhibitor and determine its effect upon adipogenesis. YHJ-7-52 reduced lipid accumulation in differentiated cells by comparable amounts as a potent hydroxamate MMPI, GM6001. However, YHJ-7-82, a non-inhibitory structural analog of YHJ-7-52, in which the zinc-binding thiol group is replaced by a hydroxyl group, had no effect on adipogenesis. The two MMPIs (YHJ-7-52 and GM6001) were also as effective in reducing lipid accumulation in differentiated cells as T0070907, an antagonist of peroxisome-proliferator activated receptor gamma (PPAR-gamma), at a similar concentration. PPAR-gamma is a typical adipogenic marker and a key regulatory protein for the transition of preadiopocyte to adipocyte. Moreover, MMP inhibition was able to suppress lipid accumulation in cells co-treated with Troglitazone, a PPAR-gamma agonist. Our results indicate that MMP inhibitors may be used as molecular tools for adipogenesis and obesity treatment research. |
| first_indexed | 2024-12-12T06:16:14Z |
| format | Article |
| id | doaj.art-7379180d37c4423d84404edb3121cd1b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T06:16:14Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7379180d37c4423d84404edb3121cd1b2022-12-22T00:35:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017292510.1371/journal.pone.0172925A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis.Dale B BoscoMark D RoycikYonghao JinMartin A SchwartzTy J LivelyDiego A R ZorioQing-Xiang Amy SangDevelopment of adipose tissue requires the differentiation of less specialized cells, such as human mesenchymal stem cells (hMSCs), into adipocytes. Since matrix metalloproteinases (MMPs) play critical roles in the cell differentiation process, we conducted investigations to determine if a novel mercaptosulfonamide-based MMP inhibitor (MMPI), YHJ-7-52, could affect hMSC adipogenic differentiation and lipid accumulation. Enzyme inhibition assays, adipogenic differentiation experiments, and quantitative PCR methods were employed to characterize this inhibitor and determine its effect upon adipogenesis. YHJ-7-52 reduced lipid accumulation in differentiated cells by comparable amounts as a potent hydroxamate MMPI, GM6001. However, YHJ-7-82, a non-inhibitory structural analog of YHJ-7-52, in which the zinc-binding thiol group is replaced by a hydroxyl group, had no effect on adipogenesis. The two MMPIs (YHJ-7-52 and GM6001) were also as effective in reducing lipid accumulation in differentiated cells as T0070907, an antagonist of peroxisome-proliferator activated receptor gamma (PPAR-gamma), at a similar concentration. PPAR-gamma is a typical adipogenic marker and a key regulatory protein for the transition of preadiopocyte to adipocyte. Moreover, MMP inhibition was able to suppress lipid accumulation in cells co-treated with Troglitazone, a PPAR-gamma agonist. Our results indicate that MMP inhibitors may be used as molecular tools for adipogenesis and obesity treatment research.http://europepmc.org/articles/PMC5325569?pdf=render |
| spellingShingle | Dale B Bosco Mark D Roycik Yonghao Jin Martin A Schwartz Ty J Lively Diego A R Zorio Qing-Xiang Amy Sang A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. PLoS ONE |
| title | A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. |
| title_full | A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. |
| title_fullStr | A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. |
| title_full_unstemmed | A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. |
| title_short | A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis. |
| title_sort | new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis |
| url | http://europepmc.org/articles/PMC5325569?pdf=render |
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