Human Periodontal Ligament Stem Cell-Derived Exosomes Promote Bone Regeneration by Altering MicroRNA Profiles

Abstract

The role and underlying mechanism of exosomes derived from human periodontal ligament stem cells (PDLSC) in osteogenesis are unclear. In the present study, we identified the exosomes derived from PDLSCs and found that osteogenic induction can enhance the osteogenic ability of PDLSC-derived exosomes in promoting the osteogenic differentiation of rat bone marrow stem cells (BMSCs). To investigate the underlying mechanism, we analyzed the exosomal miRNA expression profiles of undifferentiated and osteogenic differentiated PDLSCs by RNA sequencing. The results showed that seventy-two miRNAs were upregulated and thirty-five miRNAs were downregulated after osteogenic induction. The results of Gene Ontology analysis and pathway analysis demonstrated that the target genes of differentially expressed exosomal miRNAs participate in the regulation of a variety of biological processes, such as catalytic activity, protein binding, metabolic processes, cell development, and differentiation, and are enriched in osteogenic differentiation-related pathways, such as MAPK signaling, AMPK signaling, and insulin signaling pathways. Our results reveal for the first time that the exosomal miRNAs derived from osteogenic differentiated PDLSCs may promote the osteogenic differentiation of BMSCs, which provides a basis for further research on the regulatory function of exosomal miRNA of PDLSCs during osteogenesis.

Translational and Clinical Applications of Dental Stem Cell-Derived Exosomes

“…The exosomes isolated from PDLSCs that were exposed to the LPS-induced periodontitis environment demonstrated good anti-inflammatory ability by modulating the balance of T helper cell 17 (Th17)/regulatory T cell (Treg) through the miR-155-5p/SIRT1 pathway ( Zheng et al, 2019 ). In terms of osteogenesis, PDLSC-Exos possess the capacity for inducing osteogenic differentiation of BMMSCs via regulating AMPK signaling, MAPK signaling, and insulin signaling pathways ( Liu et al, 2020 ). P2X7R overexpressing PDLSCs-derived conditional medium and exosomes markedly improved the osteogenic capacity of PDLSCs in the inflammatory microenvironment by delivering miR-3679-5p, miR-6515-5p, and miR-6747-5p ( Xu X. Y. et al, 2020 ).…”

Dental Mesenchymal Stem Cell Secretome: An Intriguing Approach for Neuroprotection and Neuroregeneration

“…Compared with undifferentiated PDLSCs EVs, 3 circRNAs and 2 lncRNAs were upregulated and 39 circRNAs and 5 lncRNAs were downregulated consistently after 5 and 7 days of exposure to differentiation medium [ 52 ]. Moreover, 72 miRNAs were upregulated while 35 were downregulated in PDLSCs EXOs after osteogenic induction [ 53 ].…”

Maxillofacial-Derived Mesenchymal Stem Cells: Characteristics and Progress in Tissue Regeneration

“…However, scientists have now found that there are dual origins of DPSCs. Suppress: CD3 + T cells [83]; Th17 cells [84]; B cells [83]; dendritic cells [69]; M1 macrophages [203] PDLSC-CM: enhance periodontal regeneration [81] Exosomes: enhance the osteogenic ability of BMMSCs [82] Hypoxia: increase osteogenic [88] TNF-α, IL-1β: increase angiogenesis & tissue regeneration [89] DPSCs Suppress: PBMCs [114,119] (T cells [115][116][117]204], B cells [118])…”

“…PDLSC-conditioned medium (CM), which contains the paracrine factors, can enhance periodontal regeneration in rats with surgically created periodontal defects by suppressing the inflammatory response through TNF- α production [ 81 ]. Exosomes from osteogenic-inducted PDLSCs can enhance the osteogenic ability of BMMSCs [ 82 ].…”