Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway
Background: Fibro-adipogenic progenitors (FAPs) contribute to excessive muscular fatty infiltration after rotator cuff tears (RCT), impairing shoulder function. Tanshinone IIA (Tan IIA), a major active compound from Salvia miltiorrhiza Bunge, has known anti-adipogenic effects, yet its impact on FAP...
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Elsevier
2025-12-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320425001725 |
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| author | Yumei Zhang Xinghua Li Rui Zhang Minhui Wang Tihui Wang Guanfeng Liu Amila Kuati Wenhua Mao |
| author_facet | Yumei Zhang Xinghua Li Rui Zhang Minhui Wang Tihui Wang Guanfeng Liu Amila Kuati Wenhua Mao |
| author_sort | Yumei Zhang |
| collection | DOAJ |
| description | Background: Fibro-adipogenic progenitors (FAPs) contribute to excessive muscular fatty infiltration after rotator cuff tears (RCT), impairing shoulder function. Tanshinone IIA (Tan IIA), a major active compound from Salvia miltiorrhiza Bunge, has known anti-adipogenic effects, yet its impact on FAP adipogenesis remains unclear. Methods: Human FAPs from rotator cuff muscles were isolated via FACS, cultured, and treated with Tan IIA. Adipogenic differentiation was assessed with Oil Red O staining and RT-qPCR for lipid accumulation and gene expression. Single-cell RNA sequencing identified affected FAP subpopulations, while pathway analysis and Western blots confirmed Wnt/β-catenin pathway activation. β-catenin inhibitors KYA1797K and XAV-939 were then applied to evaluate pathway specificity. In vivo, RCT models received Tan IIA treatment, with Plin1 staining and triglyceride quantification measuring fatty infiltration, and gait and treadmill tests assessing shoulder function. Results: Tan IIA reduced adipogenic differentiation of FAPs in vitro, as shown by Oil Red O staining and RT-qPCR. Single-cell RNA sequencing indicated that Tan IIA reduced adipogenic potential in specific FAP populations. Enrichment analysis and Western blot results confirmed Wnt/β-catenin pathway activation by Tan IIA. Anti-adipogenic effects were reversed with β-catenin inhibitors. In vivo, Tan IIA significantly reduced muscular fatty infiltration and improved shoulder function in RCT models. Conclusion: Tan IIA inhibits FAP adipogenesis through Wnt/β-catenin signaling activation, reducing fatty infiltration and enhancing shoulder function in RCT, suggesting Tan IIA as a potential treatment. |
| format | Article |
| id | doaj-art-c876cd74eedf4dbeac955165dbeef829 |
| institution | DOAJ |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-c876cd74eedf4dbeac955165dbeef8292025-08-20T03:04:57ZengElsevierRegenerative Therapy2352-32042025-12-013058459410.1016/j.reth.2025.08.004Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathwayYumei Zhang0Xinghua Li1Rui Zhang2Minhui Wang3Tihui Wang4Guanfeng Liu5Amila Kuati6Wenhua Mao7Department of Orthopedics, XianJu People's Hospital, Zhejiang Southeast Campus of Zhejiang Provincial People's Hospital, Affiliated Xianju's Hospital, Hangzhou Medical College, Xianju, Zhejiang, 317399, ChinaDepartment of Cardiology, Fujian Medical University Union Hospital, Fuzhou, 350001, ChinaDepartment of Orthopedics, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics. School of Medical Technology and Engineering. Fujian Medical University, Fuzhou, 350122, ChinaDepartment of Orthopedics, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, ChinaDepartment of Orthopedics, XianJu People's Hospital, Zhejiang Southeast Campus of Zhejiang Provincial People's Hospital, Affiliated Xianju's Hospital, Hangzhou Medical College, Xianju, Zhejiang, 317399, China; Corresponding author.Department of Rehabilitation Medicine, Peking University Third Hospital, Beijing, 100191, China; Corresponding author.Department of Orthopedics, XianJu People's Hospital, Zhejiang Southeast Campus of Zhejiang Provincial People's Hospital, Affiliated Xianju's Hospital, Hangzhou Medical College, Xianju, Zhejiang, 317399, China; Corresponding author.Background: Fibro-adipogenic progenitors (FAPs) contribute to excessive muscular fatty infiltration after rotator cuff tears (RCT), impairing shoulder function. Tanshinone IIA (Tan IIA), a major active compound from Salvia miltiorrhiza Bunge, has known anti-adipogenic effects, yet its impact on FAP adipogenesis remains unclear. Methods: Human FAPs from rotator cuff muscles were isolated via FACS, cultured, and treated with Tan IIA. Adipogenic differentiation was assessed with Oil Red O staining and RT-qPCR for lipid accumulation and gene expression. Single-cell RNA sequencing identified affected FAP subpopulations, while pathway analysis and Western blots confirmed Wnt/β-catenin pathway activation. β-catenin inhibitors KYA1797K and XAV-939 were then applied to evaluate pathway specificity. In vivo, RCT models received Tan IIA treatment, with Plin1 staining and triglyceride quantification measuring fatty infiltration, and gait and treadmill tests assessing shoulder function. Results: Tan IIA reduced adipogenic differentiation of FAPs in vitro, as shown by Oil Red O staining and RT-qPCR. Single-cell RNA sequencing indicated that Tan IIA reduced adipogenic potential in specific FAP populations. Enrichment analysis and Western blot results confirmed Wnt/β-catenin pathway activation by Tan IIA. Anti-adipogenic effects were reversed with β-catenin inhibitors. In vivo, Tan IIA significantly reduced muscular fatty infiltration and improved shoulder function in RCT models. Conclusion: Tan IIA inhibits FAP adipogenesis through Wnt/β-catenin signaling activation, reducing fatty infiltration and enhancing shoulder function in RCT, suggesting Tan IIA as a potential treatment.http://www.sciencedirect.com/science/article/pii/S2352320425001725Rotator cuff tearsFibro-adipogenic progenitorsAdipogenesisTanshinone IIA |
| spellingShingle | Yumei Zhang Xinghua Li Rui Zhang Minhui Wang Tihui Wang Guanfeng Liu Amila Kuati Wenhua Mao Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway Regenerative Therapy Rotator cuff tears Fibro-adipogenic progenitors Adipogenesis Tanshinone IIA |
| title | Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway |
| title_full | Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway |
| title_fullStr | Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway |
| title_full_unstemmed | Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway |
| title_short | Tanshinone IIA suppresses fibro-adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via Wnt/β-catenin pathway |
| title_sort | tanshinone iia suppresses fibro adipogenic progenitor differentiation and attenuates fat infiltration in rotator cuff injury via wnt β catenin pathway |
| topic | Rotator cuff tears Fibro-adipogenic progenitors Adipogenesis Tanshinone IIA |
| url | http://www.sciencedirect.com/science/article/pii/S2352320425001725 |
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