Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis
Background: Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear. Methods: Human OA samples were used to assess CCGs expression. Cartilage-specific miR-128a kno...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Biomedical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2319417023000665 |
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| author | Jih-Yang Ko Feng-Sheng Wang Wei-Shiung Lian Hsiao-Chi Fang Shu-Jui Kuo |
| author_facet | Jih-Yang Ko Feng-Sheng Wang Wei-Shiung Lian Hsiao-Chi Fang Shu-Jui Kuo |
| author_sort | Jih-Yang Ko |
| collection | DOAJ |
| description | Background: Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear. Methods: Human OA samples were used to assess CCGs expression. Cartilage-specific miR-128a knockout mouse model was established to investigate miR-128a′s role in OA pathogenesis. Destabilization of the medial meniscus (DMM) model was employed to simulate OA. Results: Transcription levels of nuclear receptor subfamily 1 group D member 2 (NR1D2) were lower in both human OA samples and wild-type mice undergoing DMM compared to non-OA counterparts. MiR-128a knockout mice showed reduced disturbances in micro-computed tomographic and kinematic parameters following DMM, as well as less severe histologic cartilage loss. Immunohistochemistry staining revealed a lesser decrease in NR1D2-positive chondrocytes after DMM in miR-128a knockout mice than in wild-type mice. NR1D2 agonist rescued the suppressed expression of cartilage anabolic factors and extracellular matrix deposition caused by miR-128a precursor. Conclusions: Cartilage-specific miR-128a knockout mice exhibited reduced severity, less disrupted kinematic parameters, and suppressed NR1D2 expression after DMM. NR1D2 enhanced the expression of cartilage anabolic factors and extracellular matrix deposition. These findings highlight the potential of employing miR-128a and CCG-targeted therapy for knee OA. |
| first_indexed | 2024-04-24T20:12:56Z |
| format | Article |
| id | doaj.art-425b773f55b8496593539f2d49e0fd4d |
| institution | Directory Open Access Journal |
| issn | 2319-4170 |
| language | English |
| last_indexed | 2024-04-24T20:12:56Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedical Journal |
| spelling | doaj.art-425b773f55b8496593539f2d49e0fd4d2024-03-23T06:24:22ZengElsevierBiomedical Journal2319-41702024-04-01472100629Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritisJih-Yang Ko0Feng-Sheng Wang1Wei-Shiung Lian2Hsiao-Chi Fang3Shu-Jui Kuo4Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanDepartment of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, TaiwanSchool of Medicine, China Medical University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan; Corresponding author. School of Medicine, China Medical University, 91, Xueshi Rd., North Dist., Taichung 404328, Taiwan.Background: Micro-ribonucleic acids (miRNAs) are involved in osteoarthritis (OA) pathogenesis and clock-controlled genes (CCGs) regulation. However, the interaction between miRNAs and CCGs remains unclear. Methods: Human OA samples were used to assess CCGs expression. Cartilage-specific miR-128a knockout mouse model was established to investigate miR-128a′s role in OA pathogenesis. Destabilization of the medial meniscus (DMM) model was employed to simulate OA. Results: Transcription levels of nuclear receptor subfamily 1 group D member 2 (NR1D2) were lower in both human OA samples and wild-type mice undergoing DMM compared to non-OA counterparts. MiR-128a knockout mice showed reduced disturbances in micro-computed tomographic and kinematic parameters following DMM, as well as less severe histologic cartilage loss. Immunohistochemistry staining revealed a lesser decrease in NR1D2-positive chondrocytes after DMM in miR-128a knockout mice than in wild-type mice. NR1D2 agonist rescued the suppressed expression of cartilage anabolic factors and extracellular matrix deposition caused by miR-128a precursor. Conclusions: Cartilage-specific miR-128a knockout mice exhibited reduced severity, less disrupted kinematic parameters, and suppressed NR1D2 expression after DMM. NR1D2 enhanced the expression of cartilage anabolic factors and extracellular matrix deposition. These findings highlight the potential of employing miR-128a and CCG-targeted therapy for knee OA.http://www.sciencedirect.com/science/article/pii/S2319417023000665OsteoarthritismiRNA-128aNR1D2 (nuclear receptor subfamily 1 group D member 2) |
| spellingShingle | Jih-Yang Ko Feng-Sheng Wang Wei-Shiung Lian Hsiao-Chi Fang Shu-Jui Kuo Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis Biomedical Journal Osteoarthritis miRNA-128a NR1D2 (nuclear receptor subfamily 1 group D member 2) |
| title | Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis |
| title_full | Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis |
| title_fullStr | Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis |
| title_full_unstemmed | Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis |
| title_short | Cartilage-specific knockout of miRNA-128a expression normalizes the expression of circadian clock genes (CCGs) and mitigates the severity of osteoarthritis |
| title_sort | cartilage specific knockout of mirna 128a expression normalizes the expression of circadian clock genes ccgs and mitigates the severity of osteoarthritis |
| topic | Osteoarthritis miRNA-128a NR1D2 (nuclear receptor subfamily 1 group D member 2) |
| url | http://www.sciencedirect.com/science/article/pii/S2319417023000665 |
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