MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis
Abstract The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissue...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-023-03664-1 |
| _version_ | 1797863994139082752 |
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| author | Yingchun Zhu Chi Zhang Bo Jiang Qirong Dong |
| author_facet | Yingchun Zhu Chi Zhang Bo Jiang Qirong Dong |
| author_sort | Yingchun Zhu |
| collection | DOAJ |
| description | Abstract The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1β/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1β/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA. |
| first_indexed | 2024-04-09T22:45:30Z |
| format | Article |
| id | doaj.art-07a5f5a4c0724b5391a86add0a9ce0d5 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-09T22:45:30Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-07a5f5a4c0724b5391a86add0a9ce0d52023-03-22T11:52:37ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-03-0118111410.1186/s13018-023-03664-1MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritisYingchun Zhu0Chi Zhang1Bo Jiang2Qirong Dong3Department of Orthopaedic Surgery, The Second Affiliated Hospital of Soochow UniversityDepartment of Orthopedic Surgery, Ningbo First HospitalDepartment of Orthopedic Surgery, Ningbo First HospitalDepartment of Orthopaedic Surgery, The Second Affiliated Hospital of Soochow UniversityAbstract The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1β/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1β/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA.https://doi.org/10.1186/s13018-023-03664-1OsteoarthritisChondrocytesmiR-760HBEGFMatrix homeostasis |
| spellingShingle | Yingchun Zhu Chi Zhang Bo Jiang Qirong Dong MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis Journal of Orthopaedic Surgery and Research Osteoarthritis Chondrocytes miR-760 HBEGF Matrix homeostasis |
| title | MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis |
| title_full | MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis |
| title_fullStr | MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis |
| title_full_unstemmed | MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis |
| title_short | MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis |
| title_sort | mir 760 targets hbegf to control cartilage extracellular matrix degradation in osteoarthritis |
| topic | Osteoarthritis Chondrocytes miR-760 HBEGF Matrix homeostasis |
| url | https://doi.org/10.1186/s13018-023-03664-1 |
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