Detrimental alteration of mesenchymal stem cells by an articular inflammatory microenvironment results in deterioration of osteoarthritis.
BMC Med
; 21(1): 215, 2023 06 19.
Article
em En
| MEDLINE
| ID: mdl-37337188
ABSTRACT
BACKGROUND:
Articular injection of mesenchymal stem cells (MSCs) has been applied to treat knee osteoarthritis (kOA), but its clinical outcomes are controversial. This study investigated whether an articular inflammatory microenvironment (AIM) impacts MSC-based therapy in a rat model of kOA.METHODS:
The biological change of MSCs and the functional change of MSCs on chondrocytes were evaluated under AIM. The key mediator and mechanism for the AIM impact on MSC therapy were explored via gain- and loss-of-function approaches.RESULTS:
The results showed that MSCs exerted potent anti-kOA effects in vivo and in vitro, but that this therapy become chondrodestructive if a chronic AIM was present. Mechanistically, the overexpression of MMP13 in the injected MSCs via a MAPKs-AP1 signaling axis was revealed as the underlying mechanism for the detriment outcome.CONCLUSIONS:
This study thus clarifies recent clinical findings while also suggesting a means to overcome any detrimental effects of MSC-based therapy while improving its efficacy.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite do Joelho
/
Transplante de Células-Tronco Mesenquimais
/
Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
BMC Med
Assunto da revista:
MEDICINA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China