Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats
Abstract Background Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participa...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01267-2 |
| _version_ | 1798034798399193088 |
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| author | Ning Wang Xuanchen Liu Zhen Tang Xinghui Wei Hui Dong Yichao Liu Hao Wu Zhigang Wu Xiaokang Li Xue Ma Zheng Guo |
| author_facet | Ning Wang Xuanchen Liu Zhen Tang Xinghui Wei Hui Dong Yichao Liu Hao Wu Zhigang Wu Xiaokang Li Xue Ma Zheng Guo |
| author_sort | Ning Wang |
| collection | DOAJ |
| description | Abstract Background Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing. Graphical Abstract |
| first_indexed | 2024-04-11T20:48:36Z |
| format | Article |
| id | doaj.art-b79da1b05fbf4fbb863a7543287969ed |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T20:48:36Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-b79da1b05fbf4fbb863a7543287969ed2022-12-22T04:03:55ZengBMCJournal of Nanobiotechnology1477-31552022-03-0120112010.1186/s12951-022-01267-2Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic ratsNing Wang0Xuanchen Liu1Zhen Tang2Xinghui Wei3Hui Dong4Yichao Liu5Hao Wu6Zhigang Wu7Xiaokang Li8Xue Ma9Zheng Guo10Department of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Nutrition, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Orthopedics, The 63750 Hospital of People’s Liberation ArmyDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical UniversityDepartment of Orthopaedics, Tangdu Hospital, Fourth Military Medical UniversityAbstract Background Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01267-2Bone defectDiabetes mellitusExosomesMiR-140-3pPlexin B1 |
| spellingShingle | Ning Wang Xuanchen Liu Zhen Tang Xinghui Wei Hui Dong Yichao Liu Hao Wu Zhigang Wu Xiaokang Li Xue Ma Zheng Guo Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats Journal of Nanobiotechnology Bone defect Diabetes mellitus Exosomes MiR-140-3p Plexin B1 |
| title | Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats |
| title_full | Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats |
| title_fullStr | Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats |
| title_full_unstemmed | Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats |
| title_short | Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats |
| title_sort | increased bmsc exosomal mir 140 3p alleviates bone degradation and promotes bone restoration by targeting plxnb1 in diabetic rats |
| topic | Bone defect Diabetes mellitus Exosomes MiR-140-3p Plexin B1 |
| url | https://doi.org/10.1186/s12951-022-01267-2 |
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