ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3ß/ß-catenin pathway.
Mol Biol Rep
; 51(1): 421, 2024 Mar 14.
Article
en En
| MEDLINE
| ID: mdl-38483756
ABSTRACT
BACKGROUND:
Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. METHODS ANDRESULTS:
The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of ß-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3ß/ ß-catenin pathway. Nuclear ß-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo.CONCLUSIONS:
ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3ß/ ß-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Serina-Treonina Quinasas
/
Osteofito
/
Células Madre Mesenquimatosas
Límite:
Animals
Idioma:
En
Revista:
Mol Biol Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
China