Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu)
Abstract Background Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. Th...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-021-02390-x |
| _version_ | 1818932977332125696 |
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| author | Kai Nan Yuankai Zhang Xin Zhang Dong Li Yan Zhao Zhaopu Jing Kang Liu Donglong Shang Zilong Geng Lihong Fan |
| author_facet | Kai Nan Yuankai Zhang Xin Zhang Dong Li Yan Zhao Zhaopu Jing Kang Liu Donglong Shang Zilong Geng Lihong Fan |
| author_sort | Kai Nan |
| collection | DOAJ |
| description | Abstract Background Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH. Methods In vitro, we investigated the osteogenic potential of miR-378-ASCs-Exos on bone marrow stromal cells (BMSCs) by alkaline phosphatase staining and western blotting. The angiogenic effects of miR-378-ASCs-Exos on human umbilical vein endothelial cells (HUVECs) were examined by evaluating their proliferation, migration, and tube-forming analyses. We identified the underlying mechanisms of miR-378 in osteogenic and angiogenic regulation. In addition, an ONFH rat model was established to explore the effects of miR-378-ASCs-Exos through histological and immunohistochemical staining and micro-CT in vivo. Results Administration of miR-378-ASCs-Exos improved the osteogenic and angiogenic potentials of BMSCs and HUVECs. miR-378 negatively regulated the suppressor of fused (Sufu) and activated Sonic Hedgehog (Shh) signaling pathway, and recombinant Sufu protein reduced the effects triggered by miR-378-ASCs-Exos. In vivo experiments indicated that miR-378-ASCs-Exos markedly accelerated bone regeneration and angiogenesis, which inhibited the progression of ONFH. Conclusion Our study indicated that miR-378-ASCs-Exos enhances osteogenesis and angiogenesis by targeting Sufu to upregulate the Shh signaling pathway, thereby attenuating GC-induced ONFH development. |
| first_indexed | 2024-12-20T04:41:03Z |
| format | Article |
| id | doaj.art-cfe7b1ef29854560b059aa4fb5cbff07 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-20T04:41:03Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-cfe7b1ef29854560b059aa4fb5cbff072022-12-21T19:53:08ZengBMCStem Cell Research & Therapy1757-65122021-06-0112111310.1186/s13287-021-02390-xExosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu)Kai Nan0Yuankai Zhang1Xin Zhang2Dong Li3Yan Zhao4Zhaopu Jing5Kang Liu6Donglong Shang7Zilong Geng8Lihong Fan9Department of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopaedics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH. Methods In vitro, we investigated the osteogenic potential of miR-378-ASCs-Exos on bone marrow stromal cells (BMSCs) by alkaline phosphatase staining and western blotting. The angiogenic effects of miR-378-ASCs-Exos on human umbilical vein endothelial cells (HUVECs) were examined by evaluating their proliferation, migration, and tube-forming analyses. We identified the underlying mechanisms of miR-378 in osteogenic and angiogenic regulation. In addition, an ONFH rat model was established to explore the effects of miR-378-ASCs-Exos through histological and immunohistochemical staining and micro-CT in vivo. Results Administration of miR-378-ASCs-Exos improved the osteogenic and angiogenic potentials of BMSCs and HUVECs. miR-378 negatively regulated the suppressor of fused (Sufu) and activated Sonic Hedgehog (Shh) signaling pathway, and recombinant Sufu protein reduced the effects triggered by miR-378-ASCs-Exos. In vivo experiments indicated that miR-378-ASCs-Exos markedly accelerated bone regeneration and angiogenesis, which inhibited the progression of ONFH. Conclusion Our study indicated that miR-378-ASCs-Exos enhances osteogenesis and angiogenesis by targeting Sufu to upregulate the Shh signaling pathway, thereby attenuating GC-induced ONFH development.https://doi.org/10.1186/s13287-021-02390-xmiR-378ExosomesASCsONFHSufuShh signaling |
| spellingShingle | Kai Nan Yuankai Zhang Xin Zhang Dong Li Yan Zhao Zhaopu Jing Kang Liu Donglong Shang Zilong Geng Lihong Fan Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu) Stem Cell Research & Therapy miR-378 Exosomes ASCs ONFH Sufu Shh signaling |
| title | Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu) |
| title_full | Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu) |
| title_fullStr | Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu) |
| title_full_unstemmed | Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu) |
| title_short | Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu) |
| title_sort | exosomes from mirna 378 modified adipose derived stem cells prevent glucocorticoid induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting mir 378 negatively regulated suppressor of fused sufu |
| topic | miR-378 Exosomes ASCs ONFH Sufu Shh signaling |
| url | https://doi.org/10.1186/s13287-021-02390-x |
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