| _version_ | 1867019173472763905 |
|---|---|
| author | Mingyang An Feng Gao Baiqing Zhang Yidong Wu Kangkang Yu Zhongyao Li Yujie Liu Chunbao Li |
| author_facet | Mingyang An Feng Gao Baiqing Zhang Yidong Wu Kangkang Yu Zhongyao Li Yujie Liu Chunbao Li Mingyang An Feng Gao Baiqing Zhang Yidong Wu Kangkang Yu Zhongyao Li Yujie Liu Chunbao Li |
| collection | Wiley Open Access |
| contents | M2 Macrophage‐Derived TGF‐β1 Drives Tendon Fibrosis in Rodent Tendinopathy Models Mingyang An Feng Gao Baiqing Zhang Yidong Wu Kangkang Yu Zhongyao Li Yujie Liu Chunbao Li Journal of Orthopaedic Research ABSTRACT Tendinopathy is a common degenerative tendon disorder, characterized by extracellular matrix disorganization and progressive fibrosis. While macrophages play a role in fibrosis in other tissues, their specific function in tendon fibrosis remains unclear. This study aims to investigate the involvement of M2‐polarized macrophages and their secretion of transforming growth factor‐β1 (TGF‐β1) in tendon fibrosis. A chronic Achilles tendinopathy rat model was established by combining repetitive acupuncture needle puncture with treadmill overuse. Immunofluorescence and molecular biology techniques were used to assess M2 macrophage infiltration, TGF‐β1 expression, and JNK pathway activation. Pharmacological intervention was performed using GW2580 (CSF‐1R antagonist), and genetic knockout experiments were conducted in a mouse model. Results showed that the model group exhibited disrupted collagen structure and fibrotic matrix deposition in the tendon, accompanied by significant accumulation of CD206⁺ M2 macrophages and elevated TGF‐β1 expression. Immunofluorescence co‐localization revealed that TGF‐β1 was primarily produced by CD206⁺ macrophages. Activation of the JNK signaling pathway was observed. GW2580 treatment significantly reduced M2 macrophage infiltration, suppressed TGF‐β1 levels, and improved histological fibrosis scores. Genetic deletion of Tgf‐β1 in myeloid cells also alleviated fibrotic changes. In conclusion, M2 macrophage‐derived TGF‐β1 plays a crucial role in tendon fibrosis by activating the JNK signaling pathway, suggesting its potential as a therapeutic target. 10.1002/jor.70121 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/jor.70121 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_jor_70121 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | M2 Macrophage‐Derived TGF‐β1 Drives Tendon Fibrosis in Rodent Tendinopathy Models Mingyang An Feng Gao Baiqing Zhang Yidong Wu Kangkang Yu Zhongyao Li Yujie Liu Chunbao Li Journal of Orthopaedic Research M2 Macrophage‐Derived TGF‐β1 Drives Tendon Fibrosis in Rodent Tendinopathy Models Mingyang An Feng Gao Baiqing Zhang Yidong Wu Kangkang Yu Zhongyao Li Yujie Liu Chunbao Li Journal of Orthopaedic Research ABSTRACT Tendinopathy is a common degenerative tendon disorder, characterized by extracellular matrix disorganization and progressive fibrosis. While macrophages play a role in fibrosis in other tissues, their specific function in tendon fibrosis remains unclear. This study aims to investigate the involvement of M2‐polarized macrophages and their secretion of transforming growth factor‐β1 (TGF‐β1) in tendon fibrosis. A chronic Achilles tendinopathy rat model was established by combining repetitive acupuncture needle puncture with treadmill overuse. Immunofluorescence and molecular biology techniques were used to assess M2 macrophage infiltration, TGF‐β1 expression, and JNK pathway activation. Pharmacological intervention was performed using GW2580 (CSF‐1R antagonist), and genetic knockout experiments were conducted in a mouse model. Results showed that the model group exhibited disrupted collagen structure and fibrotic matrix deposition in the tendon, accompanied by significant accumulation of CD206⁺ M2 macrophages and elevated TGF‐β1 expression. Immunofluorescence co‐localization revealed that TGF‐β1 was primarily produced by CD206⁺ macrophages. Activation of the JNK signaling pathway was observed. GW2580 treatment significantly reduced M2 macrophage infiltration, suppressed TGF‐β1 levels, and improved histological fibrosis scores. Genetic deletion of Tgf‐β1 in myeloid cells also alleviated fibrotic changes. In conclusion, M2 macrophage‐derived TGF‐β1 plays a crucial role in tendon fibrosis by activating the JNK signaling pathway, suggesting its potential as a therapeutic target. 10.1002/jor.70121 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | M2 Macrophage‐Derived TGF‐β1 Drives Tendon Fibrosis in Rodent Tendinopathy Models |
| topic | Journal of Orthopaedic Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/jor.70121 |