FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways
Abstract Background The role of nuclear translocation in osteoarthritis (OA) pathogenesis has garnered increasing attention in recent years. Extensive research has demonstrated that FHL2 acts as a nuclear transmitter through interactions with other nuclear transcription factors. We aimed to investig...
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BMC
2025-04-01
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| Series: | BMC Musculoskeletal Disorders |
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| Online Access: | https://doi.org/10.1186/s12891-025-08536-9 |
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| author | Yicheng Li Fei Wang Baochao Ji Abdusami Amati Li Cao |
| author_facet | Yicheng Li Fei Wang Baochao Ji Abdusami Amati Li Cao |
| author_sort | Yicheng Li |
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| description | Abstract Background The role of nuclear translocation in osteoarthritis (OA) pathogenesis has garnered increasing attention in recent years. Extensive research has demonstrated that FHL2 acts as a nuclear transmitter through interactions with other nuclear transcription factors. We aimed to investigate the role of FHL2 in an osteoarthritis cell model. Methods OA cartilage model was established by chondrocyte-like ATDC5 cells induced by 1% insulin-transferrin-selenium and then treated with interleukin-1β (IL-1β, 10 ng/mL). Lentivirus transfection was employed to suppress the expression of FHL2. Immunofluorescence and flow cytometry were used to examine nuclear transcription and apoptosis, respectively. Western blotting was performed to analyze the expression of metabolism-related proteins, autophagy-related proteins, apoptosis-related proteins, as well as proteins associated with the NF-ĸB and mTOR pathways. Results The elevated expression of FHL2 occurred in both the cytoplasm and the nucleus. Knockdown of FHL2 could inhibit IL-1β-induced phosphorylation of NF-ĸB p65 and stabilize the extracellular matrix (ECM) by decreasing MMP-3 and MMP-13 expression, to suppress COL II degradation in chondrocyte-like ATDC5 cells. Meanwhile, the knockdown of FHL2-activated autophagy in IL-1β-treated chondrocytes through mTOR signaling, characterized by an increased LC3-II/LC3-I ratio and Beclin-1. FHL2 downregulation inhibited IL-1β-induced apoptosis by suppressing BAX and Caspase-3 expression, while enhancing BCL-2 protein levels. This mechanism may involve AKT phosphorylation and decreased expression of p-NF-ĸB p65. Conclusions FHL2 knockdown activated autophagy while suppressing inflammation, apoptosis, and ECM degradation. The mechanism underlying these processes may involve the inhibition of the mTOR and NF-ĸB signaling pathways. |
| format | Article |
| id | doaj-art-abe09bc06d1c4293af1180cbd38eb414 |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | BMC Musculoskeletal Disorders |
| spelling | doaj-art-abe09bc06d1c4293af1180cbd38eb4142025-08-20T03:04:58ZengBMCBMC Musculoskeletal Disorders1471-24742025-04-0126111110.1186/s12891-025-08536-9FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathwaysYicheng Li0Fei Wang1Baochao Ji2Abdusami Amati3Li Cao4Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University UrumqiDepartment of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University UrumqiDepartment of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University UrumqiDepartment of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University UrumqiDepartment of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University UrumqiAbstract Background The role of nuclear translocation in osteoarthritis (OA) pathogenesis has garnered increasing attention in recent years. Extensive research has demonstrated that FHL2 acts as a nuclear transmitter through interactions with other nuclear transcription factors. We aimed to investigate the role of FHL2 in an osteoarthritis cell model. Methods OA cartilage model was established by chondrocyte-like ATDC5 cells induced by 1% insulin-transferrin-selenium and then treated with interleukin-1β (IL-1β, 10 ng/mL). Lentivirus transfection was employed to suppress the expression of FHL2. Immunofluorescence and flow cytometry were used to examine nuclear transcription and apoptosis, respectively. Western blotting was performed to analyze the expression of metabolism-related proteins, autophagy-related proteins, apoptosis-related proteins, as well as proteins associated with the NF-ĸB and mTOR pathways. Results The elevated expression of FHL2 occurred in both the cytoplasm and the nucleus. Knockdown of FHL2 could inhibit IL-1β-induced phosphorylation of NF-ĸB p65 and stabilize the extracellular matrix (ECM) by decreasing MMP-3 and MMP-13 expression, to suppress COL II degradation in chondrocyte-like ATDC5 cells. Meanwhile, the knockdown of FHL2-activated autophagy in IL-1β-treated chondrocytes through mTOR signaling, characterized by an increased LC3-II/LC3-I ratio and Beclin-1. FHL2 downregulation inhibited IL-1β-induced apoptosis by suppressing BAX and Caspase-3 expression, while enhancing BCL-2 protein levels. This mechanism may involve AKT phosphorylation and decreased expression of p-NF-ĸB p65. Conclusions FHL2 knockdown activated autophagy while suppressing inflammation, apoptosis, and ECM degradation. The mechanism underlying these processes may involve the inhibition of the mTOR and NF-ĸB signaling pathways.https://doi.org/10.1186/s12891-025-08536-9FHL2IL-1βmTORNF-ĸBSignaling pathwayOsteoarthritis |
| spellingShingle | Yicheng Li Fei Wang Baochao Ji Abdusami Amati Li Cao FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways BMC Musculoskeletal Disorders FHL2 IL-1β mTOR NF-ĸB Signaling pathway Osteoarthritis |
| title | FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways |
| title_full | FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways |
| title_fullStr | FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways |
| title_full_unstemmed | FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways |
| title_short | FHL2 deteriorates IL-1β induced inflammation, apoptosis, and extracellular matrix degradation in chondrocyte-like ATDC5 cells by mTOR and NF-ĸB pathways |
| title_sort | fhl2 deteriorates il 1β induced inflammation apoptosis and extracellular matrix degradation in chondrocyte like atdc5 cells by mtor and nf qb pathways |
| topic | FHL2 IL-1β mTOR NF-ĸB Signaling pathway Osteoarthritis |
| url | https://doi.org/10.1186/s12891-025-08536-9 |
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