Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression
Abstract Background Osteoarthritis (OA) is one of the most prevalent joint disease, and there are still no effective therapeutic agents or clinical methods for the cure of this disease to date. The degradation of cartilage extracellular matrix (ECM) is a major cause of OA. Method IL-1β was used to i...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-10-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12964-019-0443-2 |
| _version_ | 1818348586706927616 |
|---|---|
| author | Biao Duan Yan Liu He Hu Fu-Guo Shi Ya-Long Liu Hao Xue Xin-Yu Yun Ming-Yu Yan Xi-Rui Han An-Fu Chen Yong Wang Zhe-Hai Li |
| author_facet | Biao Duan Yan Liu He Hu Fu-Guo Shi Ya-Long Liu Hao Xue Xin-Yu Yun Ming-Yu Yan Xi-Rui Han An-Fu Chen Yong Wang Zhe-Hai Li |
| author_sort | Biao Duan |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is one of the most prevalent joint disease, and there are still no effective therapeutic agents or clinical methods for the cure of this disease to date. The degradation of cartilage extracellular matrix (ECM) is a major cause of OA. Method IL-1β was used to induce chondrogenic degradation. Q-PCR and Western blotting were used to detect mRNA and protein level, respectively. ELISA was used to detect the secreted TNF-α and IL-6 level. Immunofluorescence was used to detect the protein level of Aggrecan, Collagen II and ki67. TUNEL and flow cytometry were used to examine cell apoptosis of chondrocytes. ChIP and luciferase assay were used to study molecular gene regulation. Osteoarthritic animal model and Safranin-O staining were used to determine the in vivo OA phenotype. Results The expression of ADAM8 was up-regulated in osteoarthritic chondrocytes. Knockdown of ADAM8 suppressed the OA phenotype in the in vitro OA cell model. ADAM8 regulated OA progression through the activation of EGFR/ERK/NF-κB signaling pathway. Inhibition of Notch signaling suppressed OA phenotype in the in vitro OA cell model. Notch signaling regulated the gene expression of ADAM8 directly via Hes1. Notch1-ADAM8 positive feedback loop promoted the progression of OA in vivo. Conclusion Notch1-ADAM8 feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression. |
| first_indexed | 2024-12-13T17:52:25Z |
| format | Article |
| id | doaj.art-9c70b84fd4324503a42d391aca2b88ef |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-13T17:52:25Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-9c70b84fd4324503a42d391aca2b88ef2022-12-21T23:36:28ZengBMCCell Communication and Signaling1478-811X2019-10-0117111710.1186/s12964-019-0443-2Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progressionBiao Duan0Yan Liu1He Hu2Fu-Guo Shi3Ya-Long Liu4Hao Xue5Xin-Yu Yun6Ming-Yu Yan7Xi-Rui Han8An-Fu Chen9Yong Wang10Zhe-Hai Li11Reproductive Center, Ganzhou People’s HospitalDepartment of Orthopedics, Inner Mongolia Medical University Third Affiliated HospitalDepartment of Orthopedics, Inner Mongolia People’s HospitalDepartment of Chinese medicine, Preventive health center of Baotou steel groupDepartment of Orthopedics, Yangling Demonstration District HospitalDepartment of Pediatric Orthopedics, Fourth Hospital of BaotouDepartment of Orthopedics, Inner Mongolia Medical University Third Affiliated HospitalDepartment of Orthopedics, Inner Mongolia Medical University Third Affiliated HospitalDepartment of Orthopedics, Peking University Third HospitalDepartment of Orthopedics, Peking University Third HospitalDepartment of Orthopedics, Peking University Third HospitalInner Mongolia Medical UniversityAbstract Background Osteoarthritis (OA) is one of the most prevalent joint disease, and there are still no effective therapeutic agents or clinical methods for the cure of this disease to date. The degradation of cartilage extracellular matrix (ECM) is a major cause of OA. Method IL-1β was used to induce chondrogenic degradation. Q-PCR and Western blotting were used to detect mRNA and protein level, respectively. ELISA was used to detect the secreted TNF-α and IL-6 level. Immunofluorescence was used to detect the protein level of Aggrecan, Collagen II and ki67. TUNEL and flow cytometry were used to examine cell apoptosis of chondrocytes. ChIP and luciferase assay were used to study molecular gene regulation. Osteoarthritic animal model and Safranin-O staining were used to determine the in vivo OA phenotype. Results The expression of ADAM8 was up-regulated in osteoarthritic chondrocytes. Knockdown of ADAM8 suppressed the OA phenotype in the in vitro OA cell model. ADAM8 regulated OA progression through the activation of EGFR/ERK/NF-κB signaling pathway. Inhibition of Notch signaling suppressed OA phenotype in the in vitro OA cell model. Notch signaling regulated the gene expression of ADAM8 directly via Hes1. Notch1-ADAM8 positive feedback loop promoted the progression of OA in vivo. Conclusion Notch1-ADAM8 feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression.http://link.springer.com/article/10.1186/s12964-019-0443-2Notch1ADAM8ECMMMP-9Osteoarthritis |
| spellingShingle | Biao Duan Yan Liu He Hu Fu-Guo Shi Ya-Long Liu Hao Xue Xin-Yu Yun Ming-Yu Yan Xi-Rui Han An-Fu Chen Yong Wang Zhe-Hai Li Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression Cell Communication and Signaling Notch1 ADAM8 ECM MMP-9 Osteoarthritis |
| title | Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression |
| title_full | Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression |
| title_fullStr | Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression |
| title_full_unstemmed | Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression |
| title_short | Notch1-ADAM8 positive feed-back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression |
| title_sort | notch1 adam8 positive feed back loop regulates the degradation of chondrogenic extracellular matrix and osteoarthritis progression |
| topic | Notch1 ADAM8 ECM MMP-9 Osteoarthritis |
| url | http://link.springer.com/article/10.1186/s12964-019-0443-2 |
| work_keys_str_mv | AT biaoduan notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT yanliu notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT hehu notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT fuguoshi notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT yalongliu notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT haoxue notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT xinyuyun notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT mingyuyan notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT xiruihan notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT anfuchen notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT yongwang notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression AT zhehaili notch1adam8positivefeedbackloopregulatesthedegradationofchondrogenicextracellularmatrixandosteoarthritisprogression |