Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1β Production Through the Inhibition of the NF-κB Signaling Pathway in Macrophages

Abstract

In the oral mechanical environment, periodontal ligament cells (PDL cells) contribute to maintaining periodontal tissue homeostasis. Recent studies showed that exosomes, which are small vesicles secreted by various types of cells, play a pivotal role in cell-to-cell communication in biological processes. We examined the secretion of exosomes from PDL cells stimulated with cyclic stretch and their role in the inflammatory response of macrophages using the human macrophage cell line THP-1 and human primary monocytes/macrophages. We prepared supernatants from human PDL cells (PDL-sup) stimulated with cyclic stretch. The treatment of macrophages with PDL-sup, but not PDL-sup from unstimulated PDL cells, inhibited the production of IL-1β in LPS/nigericin-stimulated macrophages. The pretreatment of PDL cells with GW4869, an inhibitor of exosome secretion, or siRNA for Rab27B, which controls exosome secretion, abrogated the inhibitory effects of PDL-sup. A transmission electron microscopy analysis demonstrated the existence of exosomes with diameters ranging between 30 and 100 nm in PDL-sup, suggesting that exosomes in PDL-sup contribute to this inhibition. An immunofluorescence microscopy analysis revealed that exosomes labeled with PKH67, a fluorescent dye, were incorporated by macrophages as early as 2 h after the addition of exosomes. Purified exosomes inhibited IL-1β production in LPS/nigericin-stimulated macrophages and the nuclear translocation of NF-κB as well as NF-κB p65 DNA-binding activity in LPS-stimulated macrophages, suggesting that exosomes suppress IL-1β production by inhibiting the NF-κB signaling pathway. Our results indicate that PDL cells in mechanical environments contribute to the maintenance of periodontal immune/inflammatory homeostasis by releasing exosomes.

RETRACTED ARTICLE: Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway

“…Exosomes have been shown to function as a means of intercellular communication in the body. Exosomes from PDLSCs promote bone regeneration and revascularization [7], and exosomes released in mechanical environments contribute to the maintenance of periodontal immune/inflammatory homeostasis [8]. Osteocytes are also mechanically sensitive cells and can secrete multiple biologically active factors to regulate bone remodeling.…”

Inhibitor of RAGE and glucose‑induced inflammation in bone marrow mesenchymal stem cells: Effect and mechanism of action

“…The present study assessed the effects of FPS-ZM1 on HG-stimulated inflammation in BMSCs. It was previously observed that HG conditions promoted inflammatory factors and inflammatory cytokines, such as TNF-α, IL-1β and il-6, in periodontal tissues (46,47). The present study on BMScs presented similar findings; TNF-α, IL-1β and il-6 expression was enhanced after HG stimulation, whereas these effects were inhibited by FPS-ZM1.…”

Exosomes: roles and therapeutic potential in osteoarthritis

“…110 In addition, exosomes from chondrocytes could Suppress IL-1β production via inhibiting NF-κB signaling pathway. 156 promote the chondrogenic differentiation of BMSCs by activating the Wnt/β-catenin pathway, which was related to the inhibition of GSK-3β expression by exosomal miR-8485. 111 These results supported that chondrocytes could produce exosomes that mediate cell-cell communication, which play a functional role in AC maintenance and OA pathogenesis.…”