PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus
Abstract Diabetes mellitus (DM) and osteoporosis (OP) co-morbidity (DMOP) pose major health challenges owing to their complex pathophysiological interactions. The aim of this study was to identify and validate key genes implicated in the pathogenesis of both conditions. By employing the Mfuzz time-s...
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| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-89235-2 |
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| author | Rongjin Chen Chenhui Yang Hefang Xiao Ao Yang Changshun Chen Fei Yang Bo Peng Bin Geng Yayi Xia |
| author_facet | Rongjin Chen Chenhui Yang Hefang Xiao Ao Yang Changshun Chen Fei Yang Bo Peng Bin Geng Yayi Xia |
| author_sort | Rongjin Chen |
| collection | DOAJ |
| description | Abstract Diabetes mellitus (DM) and osteoporosis (OP) co-morbidity (DMOP) pose major health challenges owing to their complex pathophysiological interactions. The aim of this study was to identify and validate key genes implicated in the pathogenesis of both conditions. By employing the Mfuzz time-series gene clustering method combined with transcriptome sequencing of patient serum, we systematically delineated gene expression patterns during the transition from a healthy state through DM to DMOP. These findings were further validated using external datasets, and a series of functional enrichment analyses, gene set enrichment analyses, and immune cell infiltration studies were conducted. Our analyses revealed a distinct progression pattern from a normal state through DM to DMOP, characterized by dynamic gene expression changes. Notably, PRKD2 emerged as a significantly downregulated gene in DMOP, highlighting its crucial role in disease pathogenesis. Further analyses revealed the involvement of PRKD2 in key signaling pathways, especially the Wnt and IL-18 pathways, which are critical for bone and glucose metabolism. Validation in cellular and animal models confirmed the role of PRKD2 in apoptosis and bone metabolism, emphasizing its therapeutic potential. In conclusion, our findings establish PRKD2 as a pivotal molecule in DMOP, offering fresh insights into its mechanisms and affirming its value as a therapeutic target. |
| format | Article |
| id | doaj-art-776d22ada9894eb78c146c7081838e7e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-776d22ada9894eb78c146c7081838e7e2025-02-09T12:33:44ZengNature PortfolioScientific Reports2045-23222025-02-0115111710.1038/s41598-025-89235-2PRKD2 as a novel target for targeting the diabetes–osteoporosis nexusRongjin Chen0Chenhui Yang1Hefang Xiao2Ao Yang3Changshun Chen4Fei Yang5Bo Peng6Bin Geng7Yayi Xia8Department of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityDepartment of Orthopedics, The Second Hospital of Lanzhou UniversityAbstract Diabetes mellitus (DM) and osteoporosis (OP) co-morbidity (DMOP) pose major health challenges owing to their complex pathophysiological interactions. The aim of this study was to identify and validate key genes implicated in the pathogenesis of both conditions. By employing the Mfuzz time-series gene clustering method combined with transcriptome sequencing of patient serum, we systematically delineated gene expression patterns during the transition from a healthy state through DM to DMOP. These findings were further validated using external datasets, and a series of functional enrichment analyses, gene set enrichment analyses, and immune cell infiltration studies were conducted. Our analyses revealed a distinct progression pattern from a normal state through DM to DMOP, characterized by dynamic gene expression changes. Notably, PRKD2 emerged as a significantly downregulated gene in DMOP, highlighting its crucial role in disease pathogenesis. Further analyses revealed the involvement of PRKD2 in key signaling pathways, especially the Wnt and IL-18 pathways, which are critical for bone and glucose metabolism. Validation in cellular and animal models confirmed the role of PRKD2 in apoptosis and bone metabolism, emphasizing its therapeutic potential. In conclusion, our findings establish PRKD2 as a pivotal molecule in DMOP, offering fresh insights into its mechanisms and affirming its value as a therapeutic target.https://doi.org/10.1038/s41598-025-89235-2Diabetes mellitusOsteoporosisGene expressionTherapeutic discoveryMolecular pathway |
| spellingShingle | Rongjin Chen Chenhui Yang Hefang Xiao Ao Yang Changshun Chen Fei Yang Bo Peng Bin Geng Yayi Xia PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus Scientific Reports Diabetes mellitus Osteoporosis Gene expression Therapeutic discovery Molecular pathway |
| title | PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus |
| title_full | PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus |
| title_fullStr | PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus |
| title_full_unstemmed | PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus |
| title_short | PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus |
| title_sort | prkd2 as a novel target for targeting the diabetes osteoporosis nexus |
| topic | Diabetes mellitus Osteoporosis Gene expression Therapeutic discovery Molecular pathway |
| url | https://doi.org/10.1038/s41598-025-89235-2 |
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