SHED-Derived Exosomes Attenuate Osteoclastogenesis to Ameliorate Apical Periodontitis in Rats

Area of Science:

• Oral Biology
• Regenerative Medicine
• Cell Biology

Background:

• Apical periodontitis (AP) involves inflammation and bone loss around the tooth root.
• Current treatments for AP may benefit from adjunctive therapies to improve outcomes.

Purpose of the Study:

• To investigate the effects of human exfoliated deciduous teeth-derived exosomes (SHED-EXOs) on osteoclastogenesis.
• To elucidate the mechanisms by which SHED-EXOs inhibit osteoclast activity.
• To evaluate the therapeutic potential of SHED-EXOs in an AP rat model.

Main Methods:

• In vitro osteoclastogenesis assays with SHED-EXOs and BMMs.
• Analysis of osteoclast markers (NFATC1, CTSK, RANKL) via gene and protein expression.
• Exosomal proteomics and osteoclast transcriptomics integrated with bioinformatics.
• In vivo AP rat model with hydrogel-encapsulated SHED-EXOs delivery.
• Micro-CT, histological, and immunohistochemical evaluations.

Main Results:

• SHED-EXOs suppressed osteoclast formation in a dose-dependent manner, downregulating NFATC1, CTSK, and RANKL.
• Multiomics analysis identified PI3K-AKT signaling as a key pathway affected by SHED-EXOs.
• In vivo studies showed SHED-EXOs reduced osteoclasts, attenuated bone resorption, and restored periapical structure.

Conclusions:

• SHED-EXOs demonstrate significant potential as a cell-free adjunctive therapy for apical periodontitis.
• Inhibition of osteoclastogenesis by SHED-EXOs may occur through PI3K-AKT pathway activation.
• Localized delivery of SHED-EXOs via hydrogel shows promise for regenerative endodontics.