Osteogenesis in human periodontal ligament stem cell sheets is enhanced by the protease-activated receptor 1 (PAR1) in vivo

Alves, Tomaz; Gasparoni, Letícia Miquelitto; Balzarini, Danilo; Albuquerque‐Souza, Emmanuel; Oliveira, Victhor de; Rovai, Emanuel Silva; Silva, José António Pereira da; Huamán-Mendoza, Aldrin; Catalani, Luiz Henrique; Sipert, Carla Renata; Holzhausen, Marinella

doi:10.1038/s41598-022-19520-x

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…Periodontal ligament stem cells (PDLSCs) and dental pulp stem cells (DPSCs) are the primary sources of the multipotent stem cells responsible for maintaining the homeostasis of dental and periodontal tissues (Krivanek et al 2020). While both DPSCs and PDLSCs can differentiate into similar cell types (e.g., osteoblasts, cementoblasts, and fibroblasts) (Alves et al 2022; Sowmya et al 2015), they are distinct populations in separate compartments (Alves et al 2022; Huang et al 2009; Krivanek et al 2020). Understanding the unique characteristics of DPSCs and PDLSCs is essential for their roles in embryonic development and regeneration of lost tissues due to dental and periodontal infections.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Yang,

Alves,

Miao

et al. 2023

J Dent Res

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The regeneration of periodontal, periapical, and pulpal tissues is a complex process requiring the direct involvement of cells derived from pluripotent stem cells in the periodontal ligament and dental pulp. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are spatially distinct with the potential to differentiate into similar functional and phenotypic cells. We aimed to identify the cell heterogeneity of DPSCs and PDLSCs and explore the differentiation potentials of their specialized organ-specific functions using single-cell transcriptomic analysis. Our results revealed 7 distinct clusters, with cluster 3 showing the highest potential for differentiation. Clusters 0 to 2 displayed features similar to fibroblasts. The trajectory route of the cell state transition from cluster 3 to clusters 0, 1, and 2 indicated the distinct nature of cell differentiation. PDLSCs had a higher proportion of cells (78.6%) at the G1 phase, while DPSCs had a higher proportion of cells at the S and G2/M phases (36.1%), mirroring the lower cell proliferation capacity of PDLSCs than DPSCs. Our study suggested the heterogeneity of stemness across PDLSCs and DPSCs, the similarities of these 2 stem cell compartments to be potentially integrated for regenerative strategies, and the distinct features between them potentially particularized for organ-specific functions of the dental pulp and periodontal ligament for a targeted regenerative dental tissue repair and other regeneration therapies.

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Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Yang,

Alves,

Miao

et al. 2023

J Dent Res

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Human periodontal ligament stem cells-derived exosomes-loaded hybrid hydrogel enhances the calvarial defect regeneration in middle-age rats

Isik

Vargel

Özgür

et al. 2023

Materials Today Communications

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Functional mechanism of miR-92b-3p in osteogenic differentiation of fibroblasts in patients with ankylosing spondylitis via the TOB1/BMP/Smad pathway

Sun

et al. 2023

J Orthop Surg Res

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Background Ankylosing spondylitis (AS) is a chronic inflammatory arthritis. Upregulation of microRNA (miR)-92b-3p is associated with enhanced osteoblastic differentiation. The current study sought to investigate the functional mechanism of miR-92b-3p in osteogenic differentiation of AS fibroblasts. Methods First, fibroblasts were isolated from AS and non-AS patients and cultured. Next, cell morphology was observed, cell proliferation was assessed and the vimentin expression pattern was determined. Alkaline phosphatase (ALP) activity and levels of osteogenic markers RUNX2, OPN, OSX, and COL I were additionally measured, followed by determination of miR-92b-3p and TOB1 levels. The binding site of miR-92b-3p and TOB1 was predicted, and their target relationship was validated. Lastly, miR-92b-3p inhibitor, si-TOB1, and the BMP/Smad signaling pathway inhibitor LDN193189 were delivered into AS fibroblasts to evaluate the osteogenic differentiation of AS fibroblasts and the activation of the BMP/Smad pathway. Results miR-92b-3p was highly expressed in AS fibroblasts. AS fibroblasts showed enhanced osteogenic differentiation and proliferation, while inhibition of miR-92b-3p suppressed osteogenic differentiation and proliferation of AS fibroblasts. miR-92b-3p targeted TOB1, and TOB1 was poorly expressed in AS fibroblasts. The concurrent downregulation of TOB1 and inhibition of miR-92b-3p elevated the levels of RUNX2, OPN, OSX, and COL I and ALP activity and further enhanced the proliferation of AS fibroblasts. The BMP/Smad pathway was activated in AS fibroblasts. Silencing miR-92b-3p could inhibit the activation of the BMP/Smad pathway by upregulating TOB1. Inhibition of the BMP/Smad pathway reduced the number of calcified nodules and hindered the osteogenic differentiation and proliferation of AS fibroblasts. Conclusion Our findings highlighted that silencing miR-92b-3p inhibited the osteogenic differentiation and proliferation of AS fibroblasts by upregulation of TOB1 and inhibition of the BMP/Smad pathway. Graphical abstract

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Osteogenesis in human periodontal ligament stem cell sheets is enhanced by the protease-activated receptor 1 (PAR1) in vivo

Cited by 3 publications

References 49 publications

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells

Human periodontal ligament stem cells-derived exosomes-loaded hybrid hydrogel enhances the calvarial defect regeneration in middle-age rats

Functional mechanism of miR-92b-3p in osteogenic differentiation of fibroblasts in patients with ankylosing spondylitis via the TOB1/BMP/Smad pathway

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