Background: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis, and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells play crucial roles in responding to these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a means of cell-cell and cell-matrix communication in biological processes. Methods: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red, and ALP staining to evaluate the functions of exosomes induced by a mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, real-time PCR, FISH, luciferase reporter assay, and western blotting assay were used to investigate the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway.

Background: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells plays crucial roles in responding these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a mean of cell-cell and cell-matrix communication in biological processes. Methods: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red and ALP staining to evaluate the functions of exosomes induced by mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, RT-PCR, FISH, luciferase reporter assay and western blotting assay were used to investigated the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway. Results: In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to human periodontal ligament stem cell (HPDLSC) proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking MS. The luciferase reporter assay demonstrated that miR-181b-5p may target Phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. PCR and western blot analyses verified that miR‐181b-5p enhanced the protein kinase B (AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and osteogenesis induced by inflammation. Conclusions: This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway, suggesting a potential mechanism for maintaining periodontal homeostasis.

Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. We designed poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL‐PLGA@P NPs). Benefiting from the high affinity of AL for hydroxyapatite, AL‐PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. Our data showed that nanoparticles could selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles could upregulate osteogenesis‐related factors (ALP, Runx‐2, BMP2) and downregulate osteoclast‐related factors (TRAP, CTSK) in vitro. With AL‐PLGA@P NPs, bone microarchitecture and bone mass were improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis‐based drug system that effectively improves bone density.This article is protected by copyright. All rights reserved

Background: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells plays crucial roles in responding these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a mean of cell-cell and cell-matrix communication in biological processes. Methods: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red and ALP staining to evaluate the functions of exosomes induced by mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, RT-PCR, FISH, luciferase reporter assay and western blotting assay were used to investigated the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway. Results: In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to human periodontal ligament stem cell (HPDLSC) proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking MS. The luciferase reporter assay demonstrated that miR-181b-5p may target Phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. PCR and western blot analyses verified that miR‐181b-5p enhanced the protein kinase B (AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and osteogenesis induced by inflammation. Conclusions: This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway, suggesting a potential mechanism for maintaining periodontal homeostasis.