Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways
Abstract Background Overproduction and activation of osteoclasts result in various bone diseases, such as osteoporosis, Paget's disease, and rheumatoid arthritis. Thus, inhibiting osteoclast formation and overactivation may effectively prevent osteoclast‐related bone diseases, especially osteop...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Rheumatology & Autoimmunity |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rai2.12088 |
| _version_ | 1797346963116523520 |
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| author | Peiru Su Xiangya Luo Chunping Zeng Lin Zhou |
| author_facet | Peiru Su Xiangya Luo Chunping Zeng Lin Zhou |
| author_sort | Peiru Su |
| collection | DOAJ |
| description | Abstract Background Overproduction and activation of osteoclasts result in various bone diseases, such as osteoporosis, Paget's disease, and rheumatoid arthritis. Thus, inhibiting osteoclast formation and overactivation may effectively prevent osteoclast‐related bone diseases, especially osteoporosis. Madecassic acid, one of the most important active ingredients in Centella asiatica, has various biological effects, but its role in osteoclastogenesis remains unknown. Methods RAW 264.7 cells were stimulated with receptor activator of nuclear factor (NF)‐κΒ ligand (RANKL, 25 ng/mL) to differentiate into multi‐nucleated osteoclasts. Subsequently, osteoclasts were treated with or without varying concentrations of madecassic acid (1, 2.5, 5, and 10 μmol/L). Results Madecassic acid significantly inhibited RANKL‐induced osteoclastogenesis in a concentration‐dependent manner. In addition, it reduced the percentage of bone resorptive area compared with the control, confirming that madecassic acid can inhibit osteoclast function. Furthermore, luciferase reporter gene studies indicate that madecassic acid could decrease the transcriptional activity of NF of activated T cells (NFAT) and NF‐κB in a dose‐dependent manner. Quantitative real‐time polymerase chain reaction results show that madecassic acid attenuated the expression of osteoclast‐associated genes, including V‐ATPase‐d2, cathepsin K, tartrate‐resistant acid phosphatase (TRAP), NFAT cytoplasmic 1 (NFATc1). Western blot analysis shows that madecassic acid inhibited RANKL‐mediated degradation of IκBα and NFATc1 expression, as well as phosphorylation of c‐Jun N‐terminal kinase (JNK) in RAW 264.7 cells. Conclusion Madecassic acid inhibited osteoclast formation and function in vitro by suppressing NF‐κB, JNK, and NFAT signaling pathways, indicating its potential as a novel drug for the treatment of osteoclast‐related bone diseases, especially osteoporosis. |
| first_indexed | 2024-03-08T11:40:34Z |
| format | Article |
| id | doaj.art-9b39a4aade35407fa6c26fb71e46ac4e |
| institution | Directory Open Access Journal |
| issn | 2767-1429 |
| language | English |
| last_indexed | 2024-03-08T11:40:34Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Rheumatology & Autoimmunity |
| spelling | doaj.art-9b39a4aade35407fa6c26fb71e46ac4e2024-01-25T06:31:12ZengWileyRheumatology & Autoimmunity2767-14292023-12-013422022910.1002/rai2.12088Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathwaysPeiru Su0Xiangya Luo1Chunping Zeng2Lin Zhou3Department of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaDepartment of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaDepartment of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaDepartment of Endocrinology, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou Guangdong ChinaAbstract Background Overproduction and activation of osteoclasts result in various bone diseases, such as osteoporosis, Paget's disease, and rheumatoid arthritis. Thus, inhibiting osteoclast formation and overactivation may effectively prevent osteoclast‐related bone diseases, especially osteoporosis. Madecassic acid, one of the most important active ingredients in Centella asiatica, has various biological effects, but its role in osteoclastogenesis remains unknown. Methods RAW 264.7 cells were stimulated with receptor activator of nuclear factor (NF)‐κΒ ligand (RANKL, 25 ng/mL) to differentiate into multi‐nucleated osteoclasts. Subsequently, osteoclasts were treated with or without varying concentrations of madecassic acid (1, 2.5, 5, and 10 μmol/L). Results Madecassic acid significantly inhibited RANKL‐induced osteoclastogenesis in a concentration‐dependent manner. In addition, it reduced the percentage of bone resorptive area compared with the control, confirming that madecassic acid can inhibit osteoclast function. Furthermore, luciferase reporter gene studies indicate that madecassic acid could decrease the transcriptional activity of NF of activated T cells (NFAT) and NF‐κB in a dose‐dependent manner. Quantitative real‐time polymerase chain reaction results show that madecassic acid attenuated the expression of osteoclast‐associated genes, including V‐ATPase‐d2, cathepsin K, tartrate‐resistant acid phosphatase (TRAP), NFAT cytoplasmic 1 (NFATc1). Western blot analysis shows that madecassic acid inhibited RANKL‐mediated degradation of IκBα and NFATc1 expression, as well as phosphorylation of c‐Jun N‐terminal kinase (JNK) in RAW 264.7 cells. Conclusion Madecassic acid inhibited osteoclast formation and function in vitro by suppressing NF‐κB, JNK, and NFAT signaling pathways, indicating its potential as a novel drug for the treatment of osteoclast‐related bone diseases, especially osteoporosis.https://doi.org/10.1002/rai2.12088madecassic acidnuclear factor‐κBosteoclastogenesisosteoclastsRANKL |
| spellingShingle | Peiru Su Xiangya Luo Chunping Zeng Lin Zhou Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways Rheumatology & Autoimmunity madecassic acid nuclear factor‐κB osteoclastogenesis osteoclasts RANKL |
| title | Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways |
| title_full | Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways |
| title_fullStr | Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways |
| title_full_unstemmed | Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways |
| title_short | Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL‐induced NF‐κB, JNK and NFAT signaling pathways |
| title_sort | madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting rankl induced nf κb jnk and nfat signaling pathways |
| topic | madecassic acid nuclear factor‐κB osteoclastogenesis osteoclasts RANKL |
| url | https://doi.org/10.1002/rai2.12088 |
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