BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity
Abstract Background Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based...
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| Format: | Article |
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BMC
2023-03-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-023-00623-8 |
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| author | Xiao-Jun Yu Ying-Guang Wang Rui Lu Xin-Zhen Guo Yun-Kun Qu Shan-Xi Wang Hao-Ran Xu Hao Kang Hong-Bo You Yong Xu |
| author_facet | Xiao-Jun Yu Ying-Guang Wang Rui Lu Xin-Zhen Guo Yun-Kun Qu Shan-Xi Wang Hao-Ran Xu Hao Kang Hong-Bo You Yong Xu |
| author_sort | Xiao-Jun Yu |
| collection | DOAJ |
| description | Abstract Background Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. Methods Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. Results A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. Conclusion Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM. |
| first_indexed | 2024-04-09T22:51:44Z |
| format | Article |
| id | doaj.art-79d1bb462c6d4c909ef38aba79d0df78 |
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| issn | 1528-3658 |
| language | English |
| last_indexed | 2024-04-09T22:51:44Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
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| series | Molecular Medicine |
| spelling | doaj.art-79d1bb462c6d4c909ef38aba79d0df782023-03-22T11:36:21ZengBMCMolecular Medicine1528-36582023-03-0129111410.1186/s10020-023-00623-8BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activityXiao-Jun Yu0Ying-Guang Wang1Rui Lu2Xin-Zhen Guo3Yun-Kun Qu4Shan-Xi Wang5Hao-Ran Xu6Hao Kang7Hong-Bo You8Yong Xu9Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyYantai Affiliated Hospital of Binzhou Medical CollegeDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. Methods Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. Results A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. Conclusion Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.https://doi.org/10.1186/s10020-023-00623-8Intervertebral disc degenerationType 1 diabetes mellitusBMP7PyroptosisNucleus pulposus cellNLRP3 inflammasome activity |
| spellingShingle | Xiao-Jun Yu Ying-Guang Wang Rui Lu Xin-Zhen Guo Yun-Kun Qu Shan-Xi Wang Hao-Ran Xu Hao Kang Hong-Bo You Yong Xu BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity Molecular Medicine Intervertebral disc degeneration Type 1 diabetes mellitus BMP7 Pyroptosis Nucleus pulposus cell NLRP3 inflammasome activity |
| title | BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity |
| title_full | BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity |
| title_fullStr | BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity |
| title_full_unstemmed | BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity |
| title_short | BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity |
| title_sort | bmp7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and nlrp3 inflammasome activity |
| topic | Intervertebral disc degeneration Type 1 diabetes mellitus BMP7 Pyroptosis Nucleus pulposus cell NLRP3 inflammasome activity |
| url | https://doi.org/10.1186/s10020-023-00623-8 |
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