PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

Abstract

Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H2O2)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H2O2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.

Efficient Light-Based Bioprinting via Rutin Nanoparticle Photoinhibitor for Advanced Biomedical Applications

“…Elevated expression levels of SOD1 (213.3% relative to the Tar group) and GPX-1 (172.6% relative to the Tar group), both enzymes directly involved in peroxide scavenging, suggest Rnps treatment enhances cellular oxidative stress resistance , (Figure O,P). Similarly, enhanced expression of PPAR-γ (148.2% relative to the Tar group), a gene linked to peroxidase activity, indicates improved antioxidant activity in cells treated with Rnps (Figure Q). FOXO3, known for its role in cell metabolism and DNA repair under oxidative stress, along with Bcl-2, a cell protector against apoptosis under external stimuli, , showed upregulated levels following Rnps treatment (FOXO3:664.1 and Bcl-2:254.0% relative to the Tar group) (Figure R,S).…”

In Vitro Insights into the Role of 7,8-Epoxy-11-Sinulariolide Acetate Isolated from Soft Coral Sinularia siaesensis in the Potential Attenuation of Inflammation and Osteoclastogenesis

“…Accumulating evidence indicates that the activation of PPAR-γ can down-regulate inflammation as well as osteoclastogenesis. It was reported that PPAR-γ agonists, including troglitazone, pioglitazone, and rosiglitazone, showed inhibitory effects on osteoclast differentiation and bone resorption activity in vitro [35][36][37][38]. Hassumi et al showed that the well-known PPAR-γ agonist rosiglitazone may be able to reduce alveolar bone loss in ligature-induced periodontitis in a rat model, by decreasing RANKL expression and inhibiting osteoclast differentiation [39].…”

Antimicrobial Peptide‐ and Dentin Matrix‐Functionalized Hydrogel for Vital Pulp Therapy via Synergistic Bacteriostasis, Immunomodulation, and Dentinogenesis

“…[63,64] PPAR𝛾-primed macrophage polarization was reported to guide dentin-pulp and cementumperiodontium-bone regeneration induced by xenogeneic dentin matrix. [65,66] PPAR𝛾 was also confirmed to redirect the metabolic homeostasis of the pulp under pathological conditions including excessive inflammation, oxidative stress, and senescence. [34,35] These studies supported our findings that TGH/DM could promote the odontogenic differentiation of inflammatory hDPSCs via PPAR𝛾 activation.…”