Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation
Abstract To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL‐1β was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor‐α (TNF‐α) and IL‐6 were measured by ELISA...
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| Format: | Article |
| Language: | English |
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Wiley
2023-11-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12738 |
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| author | Lian Ren Shi‐Gao Cheng Peng‐Cheng Kang Teng‐Fei Li Xun Li Jiong‐Zhe Xiao Dong Jiang |
| author_facet | Lian Ren Shi‐Gao Cheng Peng‐Cheng Kang Teng‐Fei Li Xun Li Jiong‐Zhe Xiao Dong Jiang |
| author_sort | Lian Ren |
| collection | DOAJ |
| description | Abstract To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL‐1β was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor‐α (TNF‐α) and IL‐6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation‐specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O‐Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL‐1β‐induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL‐1β‐induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice. |
| first_indexed | 2024-03-11T11:58:15Z |
| format | Article |
| id | doaj.art-e555d30d3485437abc4f652f531fb759 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-03-11T11:58:15Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-e555d30d3485437abc4f652f531fb7592023-11-08T12:00:32ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502023-11-0139111096110510.1002/kjm2.12738Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylationLian Ren0Shi‐Gao Cheng1Peng‐Cheng Kang2Teng‐Fei Li3Xun Li4Jiong‐Zhe Xiao5Dong Jiang6Department of Orthopedic Surgery Loudi Central Hospital Loudi ChinaDepartment of Orthopedic Surgery Loudi Central Hospital Loudi ChinaDepartment of Orthopedic Surgery Loudi Central Hospital Loudi ChinaDepartment of Orthopedic Surgery Loudi Central Hospital Loudi ChinaDepartment of Orthopedic Surgery Loudi Central Hospital Loudi ChinaDepartment of Orthopedic Surgery Loudi Central Hospital Loudi ChinaDepartment of Orthopedic Surgery Loudi Central Hospital Loudi ChinaAbstract To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL‐1β was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor‐α (TNF‐α) and IL‐6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation‐specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O‐Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL‐1β‐induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL‐1β‐induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice.https://doi.org/10.1002/kjm2.12738DNMT1LASP1methylationosteoarthritisTJP2 |
| spellingShingle | Lian Ren Shi‐Gao Cheng Peng‐Cheng Kang Teng‐Fei Li Xun Li Jiong‐Zhe Xiao Dong Jiang Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation Kaohsiung Journal of Medical Sciences DNMT1 LASP1 methylation osteoarthritis TJP2 |
| title | Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation |
| title_full | Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation |
| title_fullStr | Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation |
| title_full_unstemmed | Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation |
| title_short | Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation |
| title_sort | silenced lasp1 interacts with dnmt1 to promote tjp2 expression and attenuate articular cartilage injury in mice by suppressing tjp2 methylation |
| topic | DNMT1 LASP1 methylation osteoarthritis TJP2 |
| url | https://doi.org/10.1002/kjm2.12738 |
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