BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization
Abstract Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exo...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-024-00904-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850284731959083008 |
|---|---|
| author | Yanbin Zhang Jing Bai Bin Xiao Chunyan Li |
| author_facet | Yanbin Zhang Jing Bai Bin Xiao Chunyan Li |
| author_sort | Yanbin Zhang |
| collection | DOAJ |
| description | Abstract Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis. |
| format | Article |
| id | doaj-art-db2dc6714c164d7d850b248e058952ec |
| institution | OA Journals |
| issn | 1528-3658 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-db2dc6714c164d7d850b248e058952ec2025-08-20T01:47:29ZengBMCMolecular Medicine1528-36582024-11-0130111610.1186/s10020-024-00904-wBMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarizationYanbin Zhang0Jing Bai1Bin Xiao2Chunyan Li3Department of Spine Surgery, National Center for Orthopaedics, Capital Medical University Affiliated Beijing Jishuitan HospitalDepartment of Trauma and Joint, The Third Affiliated Hospital of Beijing University of Traditional Chinese MedicineDepartment of Spine Surgery, National Center for Orthopaedics, Capital Medical University Affiliated Beijing Jishuitan HospitalDepartment of Clinial Laboratory, Capital Medical University Affiliated Beijing Jishuitan HospitalAbstract Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis.https://doi.org/10.1186/s10020-024-00904-wExosomeBone mesenchymal stem cellsPolarizationTRIM25TREM1Ubiquitination |
| spellingShingle | Yanbin Zhang Jing Bai Bin Xiao Chunyan Li BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization Molecular Medicine Exosome Bone mesenchymal stem cells Polarization TRIM25 TREM1 Ubiquitination |
| title | BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization |
| title_full | BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization |
| title_fullStr | BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization |
| title_full_unstemmed | BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization |
| title_short | BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization |
| title_sort | bmsc derived exosomes promote osteoporosis alleviation via m2 macrophage polarization |
| topic | Exosome Bone mesenchymal stem cells Polarization TRIM25 TREM1 Ubiquitination |
| url | https://doi.org/10.1186/s10020-024-00904-w |
| work_keys_str_mv | AT yanbinzhang bmscderivedexosomespromoteosteoporosisalleviationviam2macrophagepolarization AT jingbai bmscderivedexosomespromoteosteoporosisalleviationviam2macrophagepolarization AT binxiao bmscderivedexosomespromoteosteoporosisalleviationviam2macrophagepolarization AT chunyanli bmscderivedexosomespromoteosteoporosisalleviationviam2macrophagepolarization |