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Objective: Exosomes secreted by stem cells are recognized as a critical component in tissue regeneration during stem cell‐based therapy. Considering the limited sources and bone regeneration efficiency of human periodontal ligament cells (hPDLCs), we explored whether exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED‐exo) could improve the pluripotency and regenerative potential of hPDLCs. Methods and Materials: In hPDLCs, cell proliferation, migration, cell cycle, apoptosis, and osteogenic differentiation were detected after cells were exposed to SHED‐exo (SHED‐exo group), blank (control group), or control supernatant without exo (Csup group), via CCK‐8, scratch analysis, flow cytometric, real‐time PCR, and so on. Exosomes sequencing was performed to compare and analyze miRNAs contented in SHED‐exo and hPDLC‐exo. Results: As compared to control or Csup, SHED‐exo significantly increased migration, apoptosis, and proliferation, promoted cell cycle transition from G1 to S phase in hPDLCs, and enhanced Runx2 expression and mineralization. In addition, it may be explained by the significant differences in miRNA contented in SHED‐exo and hPDLC‐exo. Conclusion: Exosomes from SHED can improve cell proliferation, migration, cell cycle, apoptosis, and osteogenic differentiation of hPDLCs, which highlights the therapeutic value of this bioactive component in the regeneration of periodontal tissues using hPDLCs in clinical practice. [ABSTRACT FROM AUTHOR]

Human periodontal ligament stem cells (hPDLSCs) sheets play an important role in periodontal tissue engineering. Low‐intensity pulsed ultrasound (LIPUS) has been reported as an effective stimulus to regulate cell biological behavior. The present study aims to explore the potential of LIPUS to promote the formation and function of hPDLSC sheets (hPDLSCSs). Hematoxylin–eosin (H&E) staining, western blot, real‐time PCR, alkaline phosphatase (ALP), and alizarin red staining were used to evaluate the formation and osteogenic effect of LIPUS on hPDLSCSs in vitro. Hydroxyapatite with or without hPDLSCSs was transplanted in the subcutaneous pockets on the back of nude mice and histological analysis was performed. H&E staining showed increased synthesis of extracellular matrix (ECM) and real‐time PCR detected a significant increase in ECM‐related genes after LIPUS treatment. In addition, LIPUS could promote the expression of osteogenic differentiation‐related genes and proteins. ALP and alizarin red staining also found LIPUS enhanced the osteogenesis of hPDLSCSs. After transplantation in vivo, more dense collagen fibers similar to periodontal ligament were regenerated. Collectively, these results indicate that LIPUS not only promotes the formation and osteogenic differentiation of hPDLSCSs but also is a potential treatment strategy for periodontal tissue engineering. [ABSTRACT FROM AUTHOR]

Through loss‐ and gain‐of‐function experiments in knockout and transgenic mice, Forkhead box O (FOXO) family transcription factors have been demonstrated to play essential roles in many biological processes, including cellular proliferation, apoptosis and differentiation. Osteogenic differentiation from mesenchymal stem cells (MSCs) into osteoblasts is a well‐organized process that is carefully guided and characterized by various factors, such as runt‐related transcription factor 2 (Runx2), β‐catenin, osteocalcin (OCN), alkaline phosphatase (ALP) and activating transcription factor 4 (ATF4). Accumulating evidence suggests multiple interactions among FOXO members and the differentiation regulatory factors listed above, resulting in an enhancement or inhibition of osteogenesis in different stages of osteogenic differentiation. To systematically and integrally understand the role of FOXOs in osteogenic differentiation and explain the contrary phenomena observed in vitro and in vivo, we herein summarized FOXO‐interacting differentiation regulatory genes/factors and following alterations in differentiation. The underlying mechanism was further discussed on the basis of binding types, sites, phases and the consequent downstream transcriptional alterations of interactions among FOXOs and differentiation regulatory factors. Interestingly, a bidirectional effect of FOXOs on balancing osteogenic differentiation was discovered in MSCs. Moreover, FOXO factors are reported to be activated or suppressed by several context‐dependent signalling inputs during differentiation, and the underlying molecular basis may offer new drug development targets for treatments of bone formation defect diseases. [ABSTRACT FROM AUTHOR]