Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA
Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound h...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/10/8694 |
| _version_ | 1797599777758642176 |
|---|---|
| author | Yi Zheng Xian Dong Xinyu Wang Jie Wang Shuo Chen Yang He Jingang An Linhai He Yi Zhang |
| author_facet | Yi Zheng Xian Dong Xinyu Wang Jie Wang Shuo Chen Yang He Jingang An Linhai He Yi Zhang |
| author_sort | Yi Zheng |
| collection | DOAJ |
| description | Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs. |
| first_indexed | 2024-03-11T03:39:08Z |
| format | Article |
| id | doaj.art-014b7fef877c485ebd5dfee95fdb7350 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:39:08Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-014b7fef877c485ebd5dfee95fdb73502023-11-18T01:40:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410869410.3390/ijms24108694Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RAYi Zheng0Xian Dong1Xinyu Wang2Jie Wang3Shuo Chen4Yang He5Jingang An6Linhai He7Yi Zhang8Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, ChinaMedication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.https://www.mdpi.com/1422-0067/24/10/8694medication-related osteonecrosis of the jawzoledronateadipose tissue-derived mesenchymal stromal cellsexosomesinterleukin-1 receptor antagonisthuman gingival fibroblasts |
| spellingShingle | Yi Zheng Xian Dong Xinyu Wang Jie Wang Shuo Chen Yang He Jingang An Linhai He Yi Zhang Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA International Journal of Molecular Sciences medication-related osteonecrosis of the jaw zoledronate adipose tissue-derived mesenchymal stromal cells exosomes interleukin-1 receptor antagonist human gingival fibroblasts |
| title | Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA |
| title_full | Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA |
| title_fullStr | Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA |
| title_full_unstemmed | Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA |
| title_short | Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA |
| title_sort | exosomes derived from adipose tissue derived mesenchymal stromal cells prevent medication related osteonecrosis of the jaw through il 1ra |
| topic | medication-related osteonecrosis of the jaw zoledronate adipose tissue-derived mesenchymal stromal cells exosomes interleukin-1 receptor antagonist human gingival fibroblasts |
| url | https://www.mdpi.com/1422-0067/24/10/8694 |
| work_keys_str_mv | AT yizheng exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT xiandong exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT xinyuwang exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT jiewang exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT shuochen exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT yanghe exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT jingangan exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT linhaihe exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra AT yizhang exosomesderivedfromadiposetissuederivedmesenchymalstromalcellspreventmedicationrelatedosteonecrosisofthejawthroughil1ra |