Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis
Background: Senile osteoporosis (SOP) seriously disturbs the life of elder people. Inhibition of autophagy can contribute to the progression of SOP. Meanwhile, Salvianic acid A (SA) could inhibit the progression of SOP, and it could regulate the autophagy. However, the relationship between SA and au...
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Elsevier
2025-07-01
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| Series: | Journal of Traditional and Complementary Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2225411025000136 |
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| author | Zhixian Xu Jun Luo Yongfa Zhang Zhenyu Zhang Jie Xu |
| author_facet | Zhixian Xu Jun Luo Yongfa Zhang Zhenyu Zhang Jie Xu |
| author_sort | Zhixian Xu |
| collection | DOAJ |
| description | Background: Senile osteoporosis (SOP) seriously disturbs the life of elder people. Inhibition of autophagy can contribute to the progression of SOP. Meanwhile, Salvianic acid A (SA) could inhibit the progression of SOP, and it could regulate the autophagy. However, the relationship between SA and autophagy in SOP remains to be further explored. Methods: Bone marrow mesenchymal stem cells (BMSCs) were isolated from senescence-accelerated mouse propensity 6 (SAMP6) mice. Then, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were performed to analyze the osteogenesis in BMSCs. Meanwhile, protein levels were investigated using Western blot. The binding between Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) and Rubicon was investigated using Co-IP. ChIP and Dual-luciferase assay were used to explore the binding between bromodomain-containing protein 4 (BRD4) and ARIH1 promoter region. Results: The levels of BRD4, Rubicon and p62 were upregulated in BMSCs from SAMP6 mice, while ARIH1, Beclin1, ATG5 and the ratio of LC3II/LC3I were downregulated. SA could promote the osteogenesis of BMSCs through mediating the autophagy. In addition, SA dose-dependently upregulated the levels of OPN, OCN and Runx2 in BMSCs from SAMP6 mice. ARIH1 could degrade Rubicon through ubiquitination, and BRD4 could transcriptionally inhibit the expression of ARIH1. Meanwhile, SA obviously promoted the autophagy and osteogenesis in BMSCs through mediation of BRD4/ARIH1/Rubicon axis. Conclusion: SA promoted osteogenic differentiation of BMSCs in senile osteoporosis through BRD4/ARIH1/Rubicon axis. Thus, our study might provide a new theoretical basis for developing the new strategies against SOP in clinic. |
| format | Article |
| id | doaj-art-a6660c3235d14f9c8769df89cebdca70 |
| institution | Kabale University |
| issn | 2225-4110 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Journal of Traditional and Complementary Medicine |
| spelling | doaj-art-a6660c3235d14f9c8769df89cebdca702025-08-20T03:32:46ZengElsevierJournal of Traditional and Complementary Medicine2225-41102025-07-0115443444510.1016/j.jtcme.2025.02.003Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axisZhixian Xu0Jun Luo1Yongfa Zhang2Zhenyu Zhang3Jie Xu4Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian Province, PR China; Department of Emergency Surgery, Fujian Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, Fujian Province, PR ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian Province, PR China; Department of Orthopedic, Fujian Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Fujian Provincial Clinical Medical Research Center for Spinal Nerve and Joint Diseases, Fuzhou, 350001, Fujian Province, PR ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian Province, PR China; Department of Emergency Surgery, Fujian Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, Fujian Province, PR ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian Province, PR ChinaShengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian Province, PR China; Department of Orthopedic, Fujian Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, 350001, Fujian Province, PR China; Fujian Provincial Clinical Medical Research Center for Spinal Nerve and Joint Diseases, Fuzhou, 350001, Fujian Province, PR China; Corresponding author. Shengli Clinical Medical College of Fujian Medical University & Department of Orthopedic, Fujian Provincial Hospital & Fuzhou University Affiliated Provincial Hospital & Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital & Fujian Provincial Clinical Medical Research Center for Spinal Nerve and Joint Diseases, No.134, East Street, Fuzhou, 350001, Fujian Province, PR China.Background: Senile osteoporosis (SOP) seriously disturbs the life of elder people. Inhibition of autophagy can contribute to the progression of SOP. Meanwhile, Salvianic acid A (SA) could inhibit the progression of SOP, and it could regulate the autophagy. However, the relationship between SA and autophagy in SOP remains to be further explored. Methods: Bone marrow mesenchymal stem cells (BMSCs) were isolated from senescence-accelerated mouse propensity 6 (SAMP6) mice. Then, Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were performed to analyze the osteogenesis in BMSCs. Meanwhile, protein levels were investigated using Western blot. The binding between Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) and Rubicon was investigated using Co-IP. ChIP and Dual-luciferase assay were used to explore the binding between bromodomain-containing protein 4 (BRD4) and ARIH1 promoter region. Results: The levels of BRD4, Rubicon and p62 were upregulated in BMSCs from SAMP6 mice, while ARIH1, Beclin1, ATG5 and the ratio of LC3II/LC3I were downregulated. SA could promote the osteogenesis of BMSCs through mediating the autophagy. In addition, SA dose-dependently upregulated the levels of OPN, OCN and Runx2 in BMSCs from SAMP6 mice. ARIH1 could degrade Rubicon through ubiquitination, and BRD4 could transcriptionally inhibit the expression of ARIH1. Meanwhile, SA obviously promoted the autophagy and osteogenesis in BMSCs through mediation of BRD4/ARIH1/Rubicon axis. Conclusion: SA promoted osteogenic differentiation of BMSCs in senile osteoporosis through BRD4/ARIH1/Rubicon axis. Thus, our study might provide a new theoretical basis for developing the new strategies against SOP in clinic.http://www.sciencedirect.com/science/article/pii/S2225411025000136Senile osteoporosisSalvianic acid AAutophagyBRD4/ARIH1/Rubicon axis |
| spellingShingle | Zhixian Xu Jun Luo Yongfa Zhang Zhenyu Zhang Jie Xu Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis Journal of Traditional and Complementary Medicine Senile osteoporosis Salvianic acid A Autophagy BRD4/ARIH1/Rubicon axis |
| title | Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis |
| title_full | Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis |
| title_fullStr | Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis |
| title_full_unstemmed | Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis |
| title_short | Salvianic acid A promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain-containing protein 4/Ariadne RBR E3 ubiquitin-protein ligase 1/Rubicon axis |
| title_sort | salvianic acid a promotes osteogenic differentiation of bone marrow mesenchymal stem cells in senile osteoporosis through bromodomain containing protein 4 ariadne rbr e3 ubiquitin protein ligase 1 rubicon axis |
| topic | Senile osteoporosis Salvianic acid A Autophagy BRD4/ARIH1/Rubicon axis |
| url | http://www.sciencedirect.com/science/article/pii/S2225411025000136 |
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