SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression
Objective The literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the fun...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-05-01
|
| Series: | Orthopaedic Surgery |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/os.13715 |
| _version_ | 1797833474483159040 |
|---|---|
| author | Xiaolei Sun Aixian Tian Peng Li Jin Zhao Xin Hou Xinlong Ma Xubo Yuan |
| author_facet | Xiaolei Sun Aixian Tian Peng Li Jin Zhao Xin Hou Xinlong Ma Xubo Yuan |
| author_sort | Xiaolei Sun |
| collection | DOAJ |
| description | Objective The literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the functions of SCIMP gene for osteoporosis, both in vitro and in vivo experiments were analyzed in depth in this integrated study. Methods The significantly differentially expressed genes of postmenopausal osteoporosis (PMOP) patients from GEO database were selected. Meanwhile, the primary target gene was also confirmed in clinically recruited individuals using ELISA method; 50 postmenopausal osteoporosis patients with a T‐score of ‐2.5 were randomly enrolled; postmenopausal women with a T‐score > −2.5 were included in the non‐osteoporotic group (including osteopenia and normal bone mineral density). The associated processes and signaling pathways were deeply investigated with GO and KEGG enrichment analysis. The downstream signaling factors including Erk‐1/2, Akt, and IkB‐related signaling pathways for the potential gene were evaluated using MG‐63 cell line; the MTT, CCK‐8, and flow cytometry assays were performed to exam MG‐63 cell viability, proliferation, as well as apoptosis, respectively, under different treatments. Results Based on the differentially expressed gene analysis for GEO database, PMOP patients displayed 845 differentially expressed genes, including 709 down‐regulated and 136 up‐regulated ones. Ten genes including SCIMP were significantly differentially expressed (at least three‐fold difference). SCIMP was the most markedly decreased in PMOP patients’ specimens. Using clinical recruited individuals, the concentration of SCIMP was 96.6 ± 20.8 ng/μL in the PMOP group compared with 168.8 ± 23.5 ng/μL in the control group (p < 0.05). At the same time, the osteoclast differentiation signaling pathway was significantly up‐regulated while hedgehogs as well as other signaling pathways were down‐regulated based on the KEGG analysis. The phosphorylation level of Akt was markedly blocked in si‐SCIMP treatment. Up‐regulation of SCIMP increased cell proliferation, inhibited cell apoptosis, and enhanced cell viability in MG‐63 cells, which was markedly rescued by AKT phosphorylation inhibitor. Finally, in vivo experiments also confirmed that the upregulation of SCIMP enhanced the structural parameters of rat trabecular bone and the osteogenic activity of bone tissue. Conclusion SCIMP plays a critical role in the pathogenesis of postmenopausal osteoporosis in women. SCIMP influences osteoclasts function through an akt‐dependent molecular pathway, and subsequently influences the equilibrium process of bone metabolism. This provides a new insight into the pathogenesis of postmenopausal osteoporosis as well as the clinical treatment of osteoporosis. |
| first_indexed | 2024-04-09T14:23:39Z |
| format | Article |
| id | doaj.art-28aa2df1ac2344c987816406511045bc |
| institution | Directory Open Access Journal |
| issn | 1757-7853 1757-7861 |
| language | English |
| last_indexed | 2024-04-09T14:23:39Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Orthopaedic Surgery |
| spelling | doaj.art-28aa2df1ac2344c987816406511045bc2023-05-04T09:56:41ZengWileyOrthopaedic Surgery1757-78531757-78612023-05-011551375138310.1111/os.13715SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis ProgressionXiaolei Sun0Aixian Tian1Peng Li2Jin Zhao3Xin Hou4Xinlong Ma5Xubo Yuan6Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering Tianjin University Tianjin ChinaDepartment of Orthopaedics Tianjin Hospital Tianjin ChinaTianjin Health Information Research Center Tianjin ChinaTianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering Tianjin University Tianjin ChinaTianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering Tianjin University Tianjin ChinaDepartment of Orthopaedics Tianjin Hospital Tianjin ChinaTianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering Tianjin University Tianjin ChinaObjective The literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the functions of SCIMP gene for osteoporosis, both in vitro and in vivo experiments were analyzed in depth in this integrated study. Methods The significantly differentially expressed genes of postmenopausal osteoporosis (PMOP) patients from GEO database were selected. Meanwhile, the primary target gene was also confirmed in clinically recruited individuals using ELISA method; 50 postmenopausal osteoporosis patients with a T‐score of ‐2.5 were randomly enrolled; postmenopausal women with a T‐score > −2.5 were included in the non‐osteoporotic group (including osteopenia and normal bone mineral density). The associated processes and signaling pathways were deeply investigated with GO and KEGG enrichment analysis. The downstream signaling factors including Erk‐1/2, Akt, and IkB‐related signaling pathways for the potential gene were evaluated using MG‐63 cell line; the MTT, CCK‐8, and flow cytometry assays were performed to exam MG‐63 cell viability, proliferation, as well as apoptosis, respectively, under different treatments. Results Based on the differentially expressed gene analysis for GEO database, PMOP patients displayed 845 differentially expressed genes, including 709 down‐regulated and 136 up‐regulated ones. Ten genes including SCIMP were significantly differentially expressed (at least three‐fold difference). SCIMP was the most markedly decreased in PMOP patients’ specimens. Using clinical recruited individuals, the concentration of SCIMP was 96.6 ± 20.8 ng/μL in the PMOP group compared with 168.8 ± 23.5 ng/μL in the control group (p < 0.05). At the same time, the osteoclast differentiation signaling pathway was significantly up‐regulated while hedgehogs as well as other signaling pathways were down‐regulated based on the KEGG analysis. The phosphorylation level of Akt was markedly blocked in si‐SCIMP treatment. Up‐regulation of SCIMP increased cell proliferation, inhibited cell apoptosis, and enhanced cell viability in MG‐63 cells, which was markedly rescued by AKT phosphorylation inhibitor. Finally, in vivo experiments also confirmed that the upregulation of SCIMP enhanced the structural parameters of rat trabecular bone and the osteogenic activity of bone tissue. Conclusion SCIMP plays a critical role in the pathogenesis of postmenopausal osteoporosis in women. SCIMP influences osteoclasts function through an akt‐dependent molecular pathway, and subsequently influences the equilibrium process of bone metabolism. This provides a new insight into the pathogenesis of postmenopausal osteoporosis as well as the clinical treatment of osteoporosis.https://doi.org/10.1111/os.13715AKT SignalingOsteoporosisPostmenopausal OsteoporosisSCIMP |
| spellingShingle | Xiaolei Sun Aixian Tian Peng Li Jin Zhao Xin Hou Xinlong Ma Xubo Yuan SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression Orthopaedic Surgery AKT Signaling Osteoporosis Postmenopausal Osteoporosis SCIMP |
| title | SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression |
| title_full | SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression |
| title_fullStr | SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression |
| title_full_unstemmed | SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression |
| title_short | SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression |
| title_sort | scimp a novel targeted gene for postmenopausal osteoporosis progression |
| topic | AKT Signaling Osteoporosis Postmenopausal Osteoporosis SCIMP |
| url | https://doi.org/10.1111/os.13715 |
| work_keys_str_mv | AT xiaoleisun scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression AT aixiantian scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression AT pengli scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression AT jinzhao scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression AT xinhou scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression AT xinlongma scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression AT xuboyuan scimpanoveltargetedgeneforpostmenopausalosteoporosisprogression |