Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA.
Int J Mol Sci
; 24(10)2023 May 12.
Article
em En
| MEDLINE
| ID: mdl-37240036
ABSTRACT
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-1ß) 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteonecrose
/
Exossomos
/
Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China