Dataset Information

Sulfasalazine disrupts the interaction between TNFα and TNFR1 thus inhibiting NF-kB signaling activation to promote bone fracture healing

ABSTRACT: Fracture is one of the most common types of traumas. It is of great necessity to explore alternative therapies to boost bone fracture healing process. The aim of this study is to elucidate the role of sulfasalazine in bone fracture healing process. The role that sulfasalazine played in osteogenesis was investigated using MC3T3-E1 in vitro and in murine femoral fracture model in vivo. Western blotting, flow cytometry, RNA sequencing, Calcein AM/PI staining, Alizarin Red S staining, ALP activity assay, transmission electron microscope (TEM), H&E staining, immunohistochemistry (IHC), immunofluorescence (IF) and Surface plasmon resonance (SPR) analysis were performed in this study. Sulfasalazine failed to elicit ferroptosis and could antagonize apoptosis in osteoblasts within acceptable dose manner. Moreover, sulfasalazine promoted osteogenic differentiation. Furthermore, sulfasalazine was identified to inhibit inflammation by declination of inflammatory biomarkers. Besides, TNFα was verified as a potential downstream target for sulfasalazine and the adverse effect of TNFα on osteogenic differentiation could be largely salvaged by sulfasalazine due to direct binding between these two molecules. RNA-seq further implied decreased transcription of genes related to NF-κB pathway in sulfasalazine-treated osteoblasts. This was further verified by dampened p65 nuclear translocation. In vivo study showed sulfasalazine could promote fracture healing as evidenced by increased callus formation and better bone remodeling both histologically and radiologically. In conclusion, sulfasalazine accelerates osteogenic differentiation in vitro and promotes bone healing in vivo, instead of inducing cell death or vitiating fracture repair process. Sulfasalazine achieves this via direct binding to and thus inhibiting TNFα, which subsequently suppresses NF-κB p65 nuclear translocation. Therefore, sulfasalazine shows a promising outcome for the treatment of bone fracture.

ORGANISM(S): Mus musculus

PROVIDER: GSE289803 | GEO | 2025/04/16

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The fracture hematoma that forms between the broken fragments of bone serves as a natural fibrin scaffold. However, there is no data regarding the differences between the micro-architectural and biological properties of hematomas formed in normally healing, delayed healing, and non-healing bone defects. Mimicking these three conditions in the rat femur, we demonstrate clear differences in fibrin clot morphology, which directly affect the gene expression pattern. Specifically, RNA-sequencing reveals that the expression of essential osteogenic genes in normally healing defects are significantly up-regulated, whereas in delayed and non-healing defects they are down-regulated. Surprisingly, there were no substantial differences between delayed and non-healing defects. Most importantly, this study demonstrates that the healing outcome has already been determined at the earliest stage of bone healing. These findings could be used to develop biomaterial scaffolds mimicking the micro-architectural properties of normally healing fracture hematoma as a treatment strategy for bone defects. The hypothesis of this study was that the micro-architectural properties of the initially formed hematoma has a significant effect on the regulation of the biological process at the fracture site, which ultimately determines the outcome of bone healing. Three different healing models were investigated - normally healing, delayed healing, and non-healing defects. The results demonstrated that the intrinsic micro-architectural properties of hematomas between those groups varied distinctly in terms of fiber diameter, porosity, and density of the formed fibrin network. Those differences influenced biological responses, as evidenced by a higher expression of osteogenic genes in normally healing compared to delayed and non-healing defects, and the failed activation of BMP-2 in non-healing defects. More importantly, our results demonstrate healing outcomes are already determined at the initial (hematoma) stage of bone healing.

Dataset Information

Sulfasalazine disrupts the interaction between TNFα and TNFR1 thus inhibiting NF-kB signaling activation to promote bone fracture healing

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets