{Reference Type}: Journal Article
{Title}: ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3β/β-catenin pathway.
{Author}: Huang Z;Huang L;Ding J;Huang Y;Huang X;Li T;
{Journal}: Mol Biol Rep
{Volume}: 51
{Issue}: 1
{Year}: 2024 Mar 14
{Factor}: 2.742
{DOI}: 10.1007/s11033-024-09336-5
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>RESULTS: </B>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 β-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-3β/ β-catenin pathway. Nuclear β-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo.<BR><B>CONCLUSIONS: </B>ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3β/ β-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.