DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression
Osteoarthritis (OA) has been considered non-reversible as articular cartilage wears down with limited repair capacity. Enhanced chondrocyte hypertrophy and increased type X collagen gene (COL10A1) expression have been associated with OA. Therefore, regulators controlling collagen X expression and ch...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-09-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304223000132 |
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| author | Jinnan Chen Fangzhou Chen Xuan Wu Huiqin Bian Chen Chen Xiaojing Zhang Ruoxuan Hei XiaotongYang Haochun Yuan Qian Wang Yaojuan Lu Longwei Qiao Qiping Zheng |
| author_facet | Jinnan Chen Fangzhou Chen Xuan Wu Huiqin Bian Chen Chen Xiaojing Zhang Ruoxuan Hei XiaotongYang Haochun Yuan Qian Wang Yaojuan Lu Longwei Qiao Qiping Zheng |
| author_sort | Jinnan Chen |
| collection | DOAJ |
| description | Osteoarthritis (OA) has been considered non-reversible as articular cartilage wears down with limited repair capacity. Enhanced chondrocyte hypertrophy and increased type X collagen gene (COL10A1) expression have been associated with OA. Therefore, regulators controlling collagen X expression and chondrocyte hypertrophy may play a role in OA intervention. Here, we investigated how Distal-less homeobox 5 (DLX5), the distal-less homeobox family member, controls murine Col10a1 gene expression and chondrocyte hypertrophy in chondrogenic cell models and its role in a murine OA model. Through qRT-PCR and Western blot analyses, we detected significantly increased levels of COL10A1 and DLX5 in hypertrophic MCT and ATDC5 cells compared to their proliferative stage. Forced expression of Dlx5 further increases, while knockdown of Dlx5 decreases COL10A1 expression in hypertrophic MCT cells. We have performed dual-luciferase reporter and ChIP assays and demonstrated that DLX5 promotes reporter activity through direct interaction with Col10a1 cis-enhancer. We established a murine OA model and detected markedly increased COL10A1 and DLX5 in the articular cartilage and subchondral bone of the OA mice compared with the controls. Notably, forced overexpression of DLX5 in hypertrophic MCT cells up-regulates RUNX2, and adjacent DLX5 and RUNX2 binding sites have previously been found within the Col10a1 cis-enhancer. Together, our data suggest that DLX5 may cooperate with RUNX2 to control cell-specific Col10a1 expression and chondrocyte hypertrophy and is involved in OA pathogenesis. |
| first_indexed | 2024-03-13T00:14:43Z |
| format | Article |
| id | doaj.art-a75b8d677be14a1bb95f982c9c99a0ce |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-13T00:14:43Z |
| publishDate | 2023-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-a75b8d677be14a1bb95f982c9c99a0ce2023-07-12T04:19:43ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-09-0110520972108DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progressionJinnan Chen0Fangzhou Chen1Xuan Wu2Huiqin Bian3Chen Chen4Xiaojing Zhang5Ruoxuan Hei6 XiaotongYang7Haochun Yuan8Qian Wang9Yaojuan Lu10Longwei Qiao11Qiping Zheng12Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Department of Pathology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Shenzhen Walgenron Bio-Pharm Co.Ltd., Shenzhen, Guangdong 518118, ChinaThe Affiliated Suzhou Hospital of Nanjing Medical University, Nanjing, Jiangsu 215008, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; Shenzhen Walgenron Bio-Pharm Co.Ltd., Shenzhen, Guangdong 518118, China; Corresponding author. Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.Osteoarthritis (OA) has been considered non-reversible as articular cartilage wears down with limited repair capacity. Enhanced chondrocyte hypertrophy and increased type X collagen gene (COL10A1) expression have been associated with OA. Therefore, regulators controlling collagen X expression and chondrocyte hypertrophy may play a role in OA intervention. Here, we investigated how Distal-less homeobox 5 (DLX5), the distal-less homeobox family member, controls murine Col10a1 gene expression and chondrocyte hypertrophy in chondrogenic cell models and its role in a murine OA model. Through qRT-PCR and Western blot analyses, we detected significantly increased levels of COL10A1 and DLX5 in hypertrophic MCT and ATDC5 cells compared to their proliferative stage. Forced expression of Dlx5 further increases, while knockdown of Dlx5 decreases COL10A1 expression in hypertrophic MCT cells. We have performed dual-luciferase reporter and ChIP assays and demonstrated that DLX5 promotes reporter activity through direct interaction with Col10a1 cis-enhancer. We established a murine OA model and detected markedly increased COL10A1 and DLX5 in the articular cartilage and subchondral bone of the OA mice compared with the controls. Notably, forced overexpression of DLX5 in hypertrophic MCT cells up-regulates RUNX2, and adjacent DLX5 and RUNX2 binding sites have previously been found within the Col10a1 cis-enhancer. Together, our data suggest that DLX5 may cooperate with RUNX2 to control cell-specific Col10a1 expression and chondrocyte hypertrophy and is involved in OA pathogenesis.http://www.sciencedirect.com/science/article/pii/S2352304223000132Chondrocyte hypertrophyCol10a1 expressionDLX5OsteoarthritisRUNX2 |
| spellingShingle | Jinnan Chen Fangzhou Chen Xuan Wu Huiqin Bian Chen Chen Xiaojing Zhang Ruoxuan Hei XiaotongYang Haochun Yuan Qian Wang Yaojuan Lu Longwei Qiao Qiping Zheng DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression Genes and Diseases Chondrocyte hypertrophy Col10a1 expression DLX5 Osteoarthritis RUNX2 |
| title | DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression |
| title_full | DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression |
| title_fullStr | DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression |
| title_full_unstemmed | DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression |
| title_short | DLX5 promotes Col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression |
| title_sort | dlx5 promotes col10a1 expression and chondrocyte hypertrophy and is involved in osteoarthritis progression |
| topic | Chondrocyte hypertrophy Col10a1 expression DLX5 Osteoarthritis RUNX2 |
| url | http://www.sciencedirect.com/science/article/pii/S2352304223000132 |
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