The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway
Abstract Background Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific me...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.1145 |
| _version_ | 1797346790761037824 |
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| author | Yuting Cheng Wenjun Jin Lin Zheng Xiaolin Huang Shanshan Luo Wei Hong Jian Liao Bancha Samruajbenjakun Chidchanok Leethanakul |
| author_facet | Yuting Cheng Wenjun Jin Lin Zheng Xiaolin Huang Shanshan Luo Wei Hong Jian Liao Bancha Samruajbenjakun Chidchanok Leethanakul |
| author_sort | Yuting Cheng |
| collection | DOAJ |
| description | Abstract Background Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) signaling pathway. Methods and results RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate‐resistant acid phosphatase staining, F‐actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti‑inflammatory bone resorption, the expression of autophagy‐related proteins and NLRP3 signaling pathway factors in pre‐OCs were evaluated by western blot analysis, and the expression of OC‑specific molecules was analyzed using reverse transcription‑quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor‐α, whereas increased Interleukin‐10. In addition, SIM inhibited LPS‐induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC‑specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3‐related proteins expression while upregulating P62 under inflammatory conditions. Conclusions SIM may reduce autophagy secretion to attenuate LPS‐induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri‐implantitis. |
| first_indexed | 2024-03-08T11:38:06Z |
| format | Article |
| id | doaj.art-345dbfa784ed42809d1afc8129da3199 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-08T11:38:06Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-345dbfa784ed42809d1afc8129da31992024-01-25T11:02:19ZengWileyImmunity, Inflammation and Disease2050-45272024-01-01121n/an/a10.1002/iid3.1145The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathwayYuting Cheng0Wenjun Jin1Lin Zheng2Xiaolin Huang3Shanshan Luo4Wei Hong5Jian Liao6Bancha Samruajbenjakun7Chidchanok Leethanakul8Faculty of Dentistry Prince of Songkla University Hat Yai ThailandSchool/Hospital of Stomatology Guizhou Medical University Guiyang ChinaSchool/Hospital of Stomatology Guizhou Medical University Guiyang ChinaHospital of Stomatology Zhongshan Guangdong ChinaSchool/Hospital of Stomatology Guizhou Medical University Guiyang ChinaKey Laboratory of Endemic and Ethnic Diseases, Ministry of Education Guizhou Medical University Guiyang ChinaSchool/Hospital of Stomatology Guizhou Medical University Guiyang ChinaFaculty of Dentistry Prince of Songkla University Hat Yai ThailandFaculty of Dentistry Prince of Songkla University Hat Yai ThailandAbstract Background Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) signaling pathway. Methods and results RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate‐resistant acid phosphatase staining, F‐actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti‑inflammatory bone resorption, the expression of autophagy‐related proteins and NLRP3 signaling pathway factors in pre‐OCs were evaluated by western blot analysis, and the expression of OC‑specific molecules was analyzed using reverse transcription‑quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor‐α, whereas increased Interleukin‐10. In addition, SIM inhibited LPS‐induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC‑specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3‐related proteins expression while upregulating P62 under inflammatory conditions. Conclusions SIM may reduce autophagy secretion to attenuate LPS‐induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri‐implantitis.https://doi.org/10.1002/iid3.1145autophagyinflammatory bone resorptionNLRP3osteoclastSimvastatin |
| spellingShingle | Yuting Cheng Wenjun Jin Lin Zheng Xiaolin Huang Shanshan Luo Wei Hong Jian Liao Bancha Samruajbenjakun Chidchanok Leethanakul The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway Immunity, Inflammation and Disease autophagy inflammatory bone resorption NLRP3 osteoclast Simvastatin |
| title | The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway |
| title_full | The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway |
| title_fullStr | The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway |
| title_full_unstemmed | The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway |
| title_short | The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway |
| title_sort | role of autophagy in sim mediated anti inflammatory osteoclastogenesis through nlrp3 signaling pathway |
| topic | autophagy inflammatory bone resorption NLRP3 osteoclast Simvastatin |
| url | https://doi.org/10.1002/iid3.1145 |
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