The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism
Introduction: Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention i...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Journal of Advanced Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000079 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850167782280265728 |
|---|---|
| author | Naibo Feng Yuanlan Ye Yiming Pan Biao Kuang Yu Du Nana Geng Cheng Chen Kaiwen Liu Li Liang Menglin Xian Yuyou Yang Xingyue Li Lin Deng Fengmei Zhang Liang Kuang Mengtian Fan Yangli Xie Fengjin Guo |
| author_facet | Naibo Feng Yuanlan Ye Yiming Pan Biao Kuang Yu Du Nana Geng Cheng Chen Kaiwen Liu Li Liang Menglin Xian Yuyou Yang Xingyue Li Lin Deng Fengmei Zhang Liang Kuang Mengtian Fan Yangli Xie Fengjin Guo |
| author_sort | Naibo Feng |
| collection | DOAJ |
| description | Introduction: Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA. Objectives: To identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA. Methods: The circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1. Results: It was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal’s.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14–3–3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity. Conclusion: CircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future. |
| format | Article |
| id | doaj-art-87bfda532eb943a693462e35b5291931 |
| institution | OA Journals |
| issn | 2090-1232 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-87bfda532eb943a693462e35b52919312025-08-20T02:21:07ZengElsevierJournal of Advanced Research2090-12322024-12-016626728410.1016/j.jare.2024.01.007The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolismNaibo Feng0Yuanlan Ye1Yiming Pan2Biao Kuang3Yu Du4Nana Geng5Cheng Chen6Kaiwen Liu7Li Liang8Menglin Xian9Yuyou Yang10Xingyue Li11Lin Deng12Fengmei Zhang13Liang Kuang14Mengtian Fan15Yangli Xie16Fengjin Guo17State Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaDepartment of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair (CBMR), State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, ChinaDepartment of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair (CBMR), State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Corresponding author at: State Key Laboratory of Ultrasound in Medicine and Engineering, School of Basic Medical Sciences, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing 400016, China.Introduction: Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA. Objectives: To identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA. Methods: The circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1. Results: It was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal’s.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14–3–3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity. Conclusion: CircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future.http://www.sciencedirect.com/science/article/pii/S2090123224000079Circubqln1OsteoarthritisXBP1sPRODHProlineCartilage |
| spellingShingle | Naibo Feng Yuanlan Ye Yiming Pan Biao Kuang Yu Du Nana Geng Cheng Chen Kaiwen Liu Li Liang Menglin Xian Yuyou Yang Xingyue Li Lin Deng Fengmei Zhang Liang Kuang Mengtian Fan Yangli Xie Fengjin Guo The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism Journal of Advanced Research Circubqln1 Osteoarthritis XBP1s PRODH Proline Cartilage |
| title | The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism |
| title_full | The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism |
| title_fullStr | The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism |
| title_full_unstemmed | The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism |
| title_short | The circUbqln1, regulated by XBP1s, interplays with 14–3–3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism |
| title_sort | circubqln1 regulated by xbp1s interplays with 14 3 3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling prodh activity and proline metabolism |
| topic | Circubqln1 Osteoarthritis XBP1s PRODH Proline Cartilage |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000079 |
| work_keys_str_mv | AT naibofeng thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yuanlanye thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yimingpan thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT biaokuang thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yudu thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT nanageng thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT chengchen thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT kaiwenliu thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT liliang thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT menglinxian thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yuyouyang thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT xingyueli thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT lindeng thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT fengmeizhang thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT liangkuang thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT mengtianfan thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yanglixie thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT fengjinguo thecircubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT naibofeng circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yuanlanye circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yimingpan circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT biaokuang circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yudu circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT nanageng circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT chengchen circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT kaiwenliu circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT liliang circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT menglinxian circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yuyouyang circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT xingyueli circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT lindeng circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT fengmeizhang circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT liangkuang circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT mengtianfan circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT yanglixie circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism AT fengjinguo circubqln1regulatedbyxbp1sinterplayswith1433ztoinhibitcollagensynthesisandpromoteosteoarthritisbycontrollingprodhactivityandprolinemetabolism |