Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells

Abstract

Human dental follicle cells (DFCs) as periodontal progenitor cells are used for studies and research in regenerative medicine and not only in dentistry. Even if innovative regenerative therapies in medicine are often considered the main research area for dental stem cells, these cells are also very useful in basic research and here, for example, for the elucidation of molecular processes in the differentiation into mineralizing cells. This article summarizes the molecular mechanisms driving osteogenic differentiation of DFCs. The positive feedback loop of bone morphogenetic protein (BMP) 2 and homeobox protein DLX3 and a signaling pathway associated with protein kinase B (AKT) and protein kinase C (PKC) are presented and further insights related to other signaling pathways such as the WNT signaling pathway are explained. Subsequently, some works are presented that have investigated epigenetic modifications and non-coding ncRNAs and their connection with the osteogenic differentiation of DFCs. In addition, studies are presented that have shown the influence of extracellular matrix molecules or fundamental biological processes such as cellular senescence on osteogenic differentiation. The putative role of factors associated with inflammatory processes, such as interleukin 8, in osteogenic differentiation is also briefly discussed. This article summarizes the most important insights into the mechanisms of osteogenic differentiation in DFCs and is intended to be a small help in the direction of new research projects in this area.

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“…Some researchers found that microRNA-935-modified BMSCs promoted the proliferation and differentiation of osteoblasts in osteoporotic rats through the secretion of extracellular vesicles carrying miR-935 targeting STAT1 ( Morsczeck, 2022 ). In terms of long noncoding RNAs (lncRNAs), knocking out TUG1 inhibited the growth, proliferation, and invasion of OSCC cells by targeting the Wnt/β-catenin signaling pathway and inducing apoptosis of OSCC cells.…”

Bone Regeneration Facilitated by Autologous Bioscaffold Material: Liquid Phase of Concentrated Growth Factor with Dental Follicle Stem Cell Loading

“…25 During osteogenic differentiation, DFCs maintain a consistent expression of osteogenic transcription factors, enhanced mineral deposition, and an upregulation of osteogenic markers. 26,27 DFCs aid periodontal repair through osteopontin (OPN)-mediated processes in inflammation. 28 They also restore regenerative capabilities to periodontal ligament stem cells under inflammatory conditions.…”

“…Derived from the dental follicle, dental follicle stem cells (DFCs) possess pluripotency, capable of differentiating into periodontal ligament cells, osteoblasts, and odontoblasts. − Comparable immunomodulatory and osteogenic properties observed in both freshly isolated and cryopreserved DFCs suggest robust cellular resilience . During osteogenic differentiation, DFCs maintain a consistent expression of osteogenic transcription factors, enhanced mineral deposition, and an upregulation of osteogenic markers. , DFCs aid periodontal repair through osteopontin (OPN)-mediated processes in inflammation . They also restore regenerative capabilities to periodontal ligament stem cells under inflammatory conditions .…”