| Residential College | false |
| Status | 已發表Published |
| Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment | |
Tan, Lihua1 ; Miao, Zhimin1; Zhao, Yuxin1; Liang, Yongkai1; Xu, Nan1; Chen, Xin1; Tu, Yanbei1,2 ; He, Chengwei1
| |
| 2024-12-09 | |
| Source Publication | Journal of Advanced Research
 |
| ISSN | 2090-1232 |
| Abstract | Introduction: Osteoporosis is an osteolytic disorder resulting from an inequilibrium between osteoblast-mediated osteogenesis and osteoclast-driven bone absorption. Safe and effective approaches for osteoporosis management are still highly demanded. Purpose: This study aimed to examine the osteoprotective effect and the mechanisms of phaseol (PHA) in vitro and in vivo. Methods: Virtual screening identified the potential inhibitors of transforming growth factor-beta-activated kinase 1 (TAK1) from coumestans. The interaction between PHA and TAK1 was investigated by molecular simulation, pronase and thermal resistance assays. The maturation and function of osteoclasts were determined using tartrate-resistant acid phosphatase staining, bone absorption and F-actin ring formation assays. The differentiation and calcification of osteoblasts were assessed by alkaline phosphatase staining and Alizarin Red S staining. The activity of related targets and pathways were detected using immunoblotting, immunofluorescence and co-immunoprecipitation assays. The in vivo osteoprotective effect of PHA was evaluated using a lipopolysaccharide (LPS)-induced mouse osteoporosis model. Results: Firstly, we confirmed that TAK1 was essential in controlling bone remodeling by regulating osteogenesis and osteoclastogenesis. Moreover, PHA, a coumestan compound predominantly present in leguminous plants, was identified as a potent TAK1 inhibitor through virtual and real experiments. Subsequently, PHA was observed to enhance osteoblast differentiation and calcification, while suppress osteoclast maturation and bone resorptive function in vitro. Mechanistically, PHA remarkably inhibited the TRAF6-TAK1 complex formation, and inhibited the activation of TAK1, MAPK and NF-κB pathways by targeting TAK1. In the in vivo study, PHA strongly attenuated bone loss, inflammatory responses, and osteoclast over-activation in lipopolysaccharide-induced osteoporosis mice. Conclusion: PHA had a dual-functional regulatory impact on osteogenesis and osteoclastogenesis by targeting TAK1, suppressing TRAF6-TAK1 complex generation, and modulating its associated signaling pathways, ultimately leading to mitigating osteoporosis. This study offered compelling evidence in favor of using PHA for preventing and managing osteoporosis as both a bone anabolic and anti-resorptive agent. |
| Keyword | Phaseol Osteogenesis Osteoclastogenesis Osteoporosis Tak1 |
| DOI | 10.1016/j.jare.2024.12.009 |
| URL | View the original |
| Language | 英語English |
| Publisher | Elsevier B.V. |
| Scopus ID | 2-s2.0-85212314240 |
| Fulltext Access | |
| Citation statistics | |
| Document Type | Journal article |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Tu, Yanbei; He, Chengwei |
| Affiliation | 1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, 999078, China 2.School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu, 212013, China |
| First Author Affilication | Institute of Chinese Medical Sciences |
| Corresponding Author Affilication | Institute of Chinese Medical Sciences |
| Recommended Citation GB/T 7714 | Tan, Lihua,Miao, Zhimin,Zhao, Yuxin,et al. Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment[J]. Journal of Advanced Research, 2024. |
| APA | Tan, Lihua., Miao, Zhimin., Zhao, Yuxin., Liang, Yongkai., Xu, Nan., Chen, Xin., Tu, Yanbei., & He, Chengwei (2024). Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment. Journal of Advanced Research. |
| MLA | Tan, Lihua,et al."Dual regulation of phaseol on osteoclast formation and osteoblast differentiation by targeting TAK1 kinase for osteoporosis treatment".Journal of Advanced Research (2024). |
| Files in This Item: | There are no files associated with this item. | |||||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment