Bone regeneration involves a complex series of stages that need proper regulation of the acute inflammatory response. Toll-like receptor 4 (TLR4) is expressed in cells necessary for bone metabolism and modulates inflammatory conditions. However, excessive TLR4 activation can lead to immune dysregulation and decreased bone mineral deposition. This study investigates the effects of inhibiting TLR4 using TAK-242 on the osteogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) under an acute inflammatory condition induced by lipopolysaccharide (LPS). BM-MSCs were obtained from rats, cultured, and evaluated to validate their characteristics. Subsequently, the cells were stimulated with LPS to induce an acute inflammatory model, followed by treatment with TAK-242 to assess its immunomodulatory effects on inflammatory responses, and osteogenic differentiation. TAK-242 exhibited significant anti-inflammatory effects on LPS-stimulated cells, with decreased expressions of IL-6 (p < 0.01), TNF-α (p < 0.0001), and MMP-13 (p < 0.0001) and increased expression of TGF-β (p < 0.0001) compared to LPS-only treatment cells. Notably, the TAK-242 treatment group exhibited a decrease in osteogenic differentiation compared to the LPS-only treatment group in the early stage. This was evidenced by reduced formation of mineralized nodules and decreased expression of CoL1A1 (p < 0.0001). However, RUNX-2, ALP, and OCN expression levels did not significantly reduce, indicating that TAK-242 did not impede the process of osteogenesis. These findings emphasize the possible therapeutic use of TAK-242 in the field of osteoimmunology, particularly for treating inflammatory bone conditions.
Ghiasvand et al. (Thu,) studied this question.