Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression
Abstract Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physio...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01823-4 |
| _version_ | 1827982915722543104 |
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| author | Yunhao Wang Genjiang Zheng Xiaoxing Xie Wei Yu Jianxi Wang Fazhi Zang Chen Yang Qiangqiang Xiao Rongcheng Zhang Leixin Wei Xiaodong Wu Lei Liang Peng Cao Chen Xu Jing Li Bo Hu Tao Zhang Jinglei Wu Huajiang Chen |
| author_facet | Yunhao Wang Genjiang Zheng Xiaoxing Xie Wei Yu Jianxi Wang Fazhi Zang Chen Yang Qiangqiang Xiao Rongcheng Zhang Leixin Wei Xiaodong Wu Lei Liang Peng Cao Chen Xu Jing Li Bo Hu Tao Zhang Jinglei Wu Huajiang Chen |
| author_sort | Yunhao Wang |
| collection | DOAJ |
| description | Abstract Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physiological level and activate the skeletal interoception. Here, as nano fibers have been extensively used in the treatment of IDD, novel polycaprolactone (PCL) nano fibers loaded with low-dose celecoxib were fabricated for IDD treatment. In vitro studies demonstrated that the nano fibers had the ability of releasing low-dose celecoxib slowly and sustainably and maintain PGE2. Meanwhile, in a puncture-induced rabbit IDD model, the nano fibers reversed IDD. Furthermore, low-dose celecoxib released from the nano fibers was firstly proved to promote CHSY3 expression. In a lumbar spine instability-induced mouse IDD model, low-dose celecoxib inhibited IDD in CHSY3wt mice rather than CHSY3−/− mice. This model indicated that CHSY3 was indispensable for low-dose celecoxib to alleviate IDD. In conclusion, this study developed a novel low-dose celecoxib-loaded PCL nano fibers to reverse IDD by maintaining PGE2 at the physiological level and promoting CHSY3 expression. |
| first_indexed | 2024-04-09T22:39:29Z |
| format | Article |
| id | doaj.art-90e91fc4ac5a4e69b7ac88f0d7c3685f |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-09T22:39:29Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-90e91fc4ac5a4e69b7ac88f0d7c3685f2023-03-22T12:16:51ZengBMCJournal of Nanobiotechnology1477-31552023-03-0121111810.1186/s12951-023-01823-4Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expressionYunhao Wang0Genjiang Zheng1Xiaoxing Xie2Wei Yu3Jianxi Wang4Fazhi Zang5Chen Yang6Qiangqiang Xiao7Rongcheng Zhang8Leixin Wei9Xiaodong Wu10Lei Liang11Peng Cao12Chen Xu13Jing Li14Bo Hu15Tao Zhang16Jinglei Wu17Huajiang Chen18Spine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversityEngineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversityDepartment of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua UniversitySpine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical UniversityAbstract Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physiological level and activate the skeletal interoception. Here, as nano fibers have been extensively used in the treatment of IDD, novel polycaprolactone (PCL) nano fibers loaded with low-dose celecoxib were fabricated for IDD treatment. In vitro studies demonstrated that the nano fibers had the ability of releasing low-dose celecoxib slowly and sustainably and maintain PGE2. Meanwhile, in a puncture-induced rabbit IDD model, the nano fibers reversed IDD. Furthermore, low-dose celecoxib released from the nano fibers was firstly proved to promote CHSY3 expression. In a lumbar spine instability-induced mouse IDD model, low-dose celecoxib inhibited IDD in CHSY3wt mice rather than CHSY3−/− mice. This model indicated that CHSY3 was indispensable for low-dose celecoxib to alleviate IDD. In conclusion, this study developed a novel low-dose celecoxib-loaded PCL nano fibers to reverse IDD by maintaining PGE2 at the physiological level and promoting CHSY3 expression.https://doi.org/10.1186/s12951-023-01823-4Intervertebral disc degenerationLow-dose celecoxibPGE2CHSY3 |
| spellingShingle | Yunhao Wang Genjiang Zheng Xiaoxing Xie Wei Yu Jianxi Wang Fazhi Zang Chen Yang Qiangqiang Xiao Rongcheng Zhang Leixin Wei Xiaodong Wu Lei Liang Peng Cao Chen Xu Jing Li Bo Hu Tao Zhang Jinglei Wu Huajiang Chen Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression Journal of Nanobiotechnology Intervertebral disc degeneration Low-dose celecoxib PGE2 CHSY3 |
| title | Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression |
| title_full | Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression |
| title_fullStr | Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression |
| title_full_unstemmed | Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression |
| title_short | Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression |
| title_sort | low dose celecoxib loaded pcl fibers reverse intervertebral disc degeneration by up regulating chsy3 expression |
| topic | Intervertebral disc degeneration Low-dose celecoxib PGE2 CHSY3 |
| url | https://doi.org/10.1186/s12951-023-01823-4 |
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