Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis
| العنوان: | Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
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| المؤلفون: | Jie Zhang, Yulong Huo, Yusheng Qiu, Qiang Xu, Zhibiao Gao, Lei Wang |
| المصدر: | Cell Biology International |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Regular Issue, Osteolysis, MAP Kinase Signaling System, Osteoclasts, Inflammation, Bone tissue, abnormal osteoclastogenesis, Bone and Bones, Bone resorption, Proinflammatory cytokine, Mice, 03 medical and health sciences, 0302 clinical medicine, titanium (Ti) wear particles, Osteogenesis, Osteoclast, RAW 264.7 cell morphology, Autophagy, medicine, Animals, Humans, Research Articles, Titanium, Mice, Inbred BALB C, biology, Tartrate-Resistant Acid Phosphatase, Chemistry, Macrophages, the air pouch model of bone resorption, Cell Differentiation, Cell Biology, General Medicine, Netrin-1, medicine.disease, ERK1/2 signaling pathway, Cell biology, HEK293 Cells, RAW 264.7 Cells, 030104 developmental biology, medicine.anatomical_structure, Netrin‐1, RANKL, 030220 oncology & carcinogenesis, biology.protein, Female, medicine.symptom |
| الوصف: | Background Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this study was to investigate the molecular mechanism of osteoclast formation and dissolution induced by wear particles and the potential roles of Netrin-1, the ERK1/2 pathway and autophagy activation in this process. Methods The mRNA levels in cells and tissues were detected with real-time quantitative PCR. Western blotting was used to detect the expression of proteins. A CCK-8 kit was used to detect the viability of RAW 264.7 cells. Moreover, an air pouch model of bone resorption was established. Immunohistochemistry was used to detect the expression of TRAP and Netrin-1 in rat bone tissue. Cell culture supernatants were collected in the rat air pouch model of bone resorption, and the levels of RANKL and OPG were detected with ELISA. The protein levels of TRAP and Netrin-1 in bone tissue were examined by immunohistochemistry. Results Titanium wear particles induced osteoclast formation and autophagy activation. Moreover, blocking autophagy suppressed the osteoclastogenesis after exposure to wear particles in vitro. The activation of the ERK1/2 pathway and the overexpression of Netrin-1 were both found to play important roles in osteoclastogenesis mediated by autophagy. Moreover, 3-MA effectively decreased the secretion of proinflammatory cytokines mediated by wear particles. Conclusion Blockade of autophagy inhibits the osteoclastogenesis and inflammation induced by wear particles, thus potentially providing novel treatment strategies for abnormal osteoclastogenesis and aseptic prosthesis loosening induced by wear particles. This article is protected by copyright. All rights reserved. |
| تدمد: | 1095-8355 1065-6995 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::441a17d097460ea28e74338340dea501Test https://doi.org/10.1002/cbin.11544Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....441a17d097460ea28e74338340dea501 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10958355 10656995 |
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