Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis
Human bone marrow stem cells (hBMSCs) play an important role during the fracture healing phase. Previous clinical studies by our research group found that fracture healing time was obviously delayed in patients who underwent splenectomy, for combined traumatic fractures and splenic rupture, which is...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2025-01-01
|
| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0601 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832087208305098752 |
|---|---|
| author | Feifei Ni Jianjun Li Qin Yin Yangyang Chen Zengwu Shao Hong Wang |
| author_facet | Feifei Ni Jianjun Li Qin Yin Yangyang Chen Zengwu Shao Hong Wang |
| author_sort | Feifei Ni |
| collection | DOAJ |
| description | Human bone marrow stem cells (hBMSCs) play an important role during the fracture healing phase. Previous clinical studies by our research group found that fracture healing time was obviously delayed in patients who underwent splenectomy, for combined traumatic fractures and splenic rupture, which is most likely related to the dysregulation of immune inflammatory function of the body after splenectomy. A large number of studies have reported that the inflammatory factor interleukin-1β plays an important role in the multi-directional differentiation ability and immune regulation of BMSC, but its specific regulatory mechanism needs to be further studied. Recently, long noncoding RNAs (lncRNAs) have attracted remarkable attention owing to their close relationship with stem cell osteogenesis and potential role in various bone diseases. In this study, we explored the molecular mechanism of a novel lncRNA, LncMSTRG.11341.25 (LncMSTRG25), in terms of its effects on osteogenic differentiation of hBMSCs. Our results reveal significant up-regulation of LncMSTRG25, osteogenic differentiation markers during the osteogenic differentiation of hBMSCs, and decreased expression of miR-939-5p with an increase in differentiation time. LncMSTRG25 knockdown significantly inhibited the osteogenic ability of hBMSCs. When we knocked down PAX8 alone, we found that the osteogenic ability of hBMSCs was also significantly reduced. The interaction between LncMSTRG25 and PAX8 was verified using the RNA immunoprecipitation assay, RNA pull-down assays, silver staining, and the dual-luciferase reporter. The results show that LncMSTRG25 can function as a sponge to adsorb miR-939-5p, inducing the osteogenic differentiation of hBMSCs by activating PAX8. These findings deepen our understanding of the regulatory role of lncRNA–miRNA–mRNA networks in the immune microenvironment of bone marrow, and highlight the important role played by the spleen as an immune organ in fracture healing. |
| format | Article |
| id | doaj-art-2ce238a0b20147a29c4e32671ba1b370 |
| institution | Kabale University |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-2ce238a0b20147a29c4e32671ba1b3702025-02-06T06:23:43ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0601Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 AxisFeifei Ni0Jianjun Li1Qin Yin2Yangyang Chen3Zengwu Shao4Hong Wang5Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi 214000, Jiangsu, China.Department of Orthopedic, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Human bone marrow stem cells (hBMSCs) play an important role during the fracture healing phase. Previous clinical studies by our research group found that fracture healing time was obviously delayed in patients who underwent splenectomy, for combined traumatic fractures and splenic rupture, which is most likely related to the dysregulation of immune inflammatory function of the body after splenectomy. A large number of studies have reported that the inflammatory factor interleukin-1β plays an important role in the multi-directional differentiation ability and immune regulation of BMSC, but its specific regulatory mechanism needs to be further studied. Recently, long noncoding RNAs (lncRNAs) have attracted remarkable attention owing to their close relationship with stem cell osteogenesis and potential role in various bone diseases. In this study, we explored the molecular mechanism of a novel lncRNA, LncMSTRG.11341.25 (LncMSTRG25), in terms of its effects on osteogenic differentiation of hBMSCs. Our results reveal significant up-regulation of LncMSTRG25, osteogenic differentiation markers during the osteogenic differentiation of hBMSCs, and decreased expression of miR-939-5p with an increase in differentiation time. LncMSTRG25 knockdown significantly inhibited the osteogenic ability of hBMSCs. When we knocked down PAX8 alone, we found that the osteogenic ability of hBMSCs was also significantly reduced. The interaction between LncMSTRG25 and PAX8 was verified using the RNA immunoprecipitation assay, RNA pull-down assays, silver staining, and the dual-luciferase reporter. The results show that LncMSTRG25 can function as a sponge to adsorb miR-939-5p, inducing the osteogenic differentiation of hBMSCs by activating PAX8. These findings deepen our understanding of the regulatory role of lncRNA–miRNA–mRNA networks in the immune microenvironment of bone marrow, and highlight the important role played by the spleen as an immune organ in fracture healing.https://spj.science.org/doi/10.34133/research.0601 |
| spellingShingle | Feifei Ni Jianjun Li Qin Yin Yangyang Chen Zengwu Shao Hong Wang Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis Research |
| title | Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis |
| title_full | Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis |
| title_fullStr | Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis |
| title_full_unstemmed | Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis |
| title_short | Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis |
| title_sort | novel lncrna lncmstrg 11341 25 promotes osteogenic differentiation of human bone marrow stem cells via the mir 939 5p pax8 axis |
| url | https://spj.science.org/doi/10.34133/research.0601 |
| work_keys_str_mv | AT feifeini novellncrnalncmstrg1134125promotesosteogenicdifferentiationofhumanbonemarrowstemcellsviathemir9395ppax8axis AT jianjunli novellncrnalncmstrg1134125promotesosteogenicdifferentiationofhumanbonemarrowstemcellsviathemir9395ppax8axis AT qinyin novellncrnalncmstrg1134125promotesosteogenicdifferentiationofhumanbonemarrowstemcellsviathemir9395ppax8axis AT yangyangchen novellncrnalncmstrg1134125promotesosteogenicdifferentiationofhumanbonemarrowstemcellsviathemir9395ppax8axis AT zengwushao novellncrnalncmstrg1134125promotesosteogenicdifferentiationofhumanbonemarrowstemcellsviathemir9395ppax8axis AT hongwang novellncrnalncmstrg1134125promotesosteogenicdifferentiationofhumanbonemarrowstemcellsviathemir9395ppax8axis |