Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function
| Autor: | Hana Lee, Hye In Lee, Hansung Kim, Donghyun Hwang, Dongmin Kang, Eun Kyoung Seo, Minjeong Kwon, Jiae Lee, Woojin Jeong, Narae Kim, Nam Young Kim, Donglan Piao, Hyun Jin Kim, Gong Rak Lee |
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| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Integrin ATG5 Osteoclasts Inflammation Biochemistry Lactones Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Osteoclast Lysosome Genetics medicine Animals Secretion Bone Resorption Molecular Biology Cells Cultured NFATC Transcription Factors biology Chemistry Macrophages Cell Differentiation Cell biology Resorption 030104 developmental biology medicine.anatomical_structure biology.protein Female medicine.symptom Lysosomes Sesquiterpenes 030217 neurology & neurosurgery Biogenesis Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 33:9685-9694 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201900862r |
| Popis: | Excessive osteoclast activity can lead to an imbalance between the synthesis and breakdown of bone, with pathologic consequences that include osteoporosis and periodontitis. Thus, controlling osteoclast differentiation and function has significant therapeutic implications. In this study, we investigated the effects of dehydrocostus lactone (DL) on osteoclast differentiation and activation and elucidated the possible mechanisms underlying these processes. DL suppressed osteoclast differentiation by reducing the expression of the nuclear factor of activated T-cells, cytoplasmic 1. When used to challenge differentiated osteoclasts, DL also effectively inhibited their enlargement and resorption activity, and biochemical approaches revealed that DL attenuates osteoclast activation by inhibiting the migration and lysosome biogenesis and secretion via the down-regulation of integrin β3, PKC-β, and autophagy related 5 expression. Furthermore, DL prevented bone destruction in inflammation- and ovariectomy-induced osteolytic mouse models. These results indicate that DL has therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.-Lee, H. I., Lee, J., Hwang, D., Lee, G.-R., Kim, N., Kwon, M., Lee, H., Piao, D., Kim, H. J., Kim, N. Y., Kim, H. S., Seo, E. K., Kang, D., Jeong, W. Dehydrocostus lactone suppresses osteoclast differentiation by regulating NFATc1 and inhibits osteoclast activation through modulating migration and lysosome function. |
| Databáze: | OpenAIRE |
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