Hertwig's epithelial root sheath (HERS) cells participate in cementum formation through epithelial-mesenchymal transition (EMT). Previous studies have shown that transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF2) are involved in inducing EMT. However, their involvement in HERS cell transition remains elusive. In this study, we confirmed that HERS cells underwent EMT during the formation of acellular cementum. We found that both TGF-β1 and FGF2 stimulated the EMT of HERS cells. The TGF-β1 regulated the differentiation of HERS cells into periodontal ligament fibroblast-like cells, and FGF2 directed the differentiation of HERS cells into cementoblast-like cells. Treatment with TGF-β1 or FGF2 inhibitor could effectively suppress HERS cells differential transition. Combined stimulation with both TGF-β1 and FGF-2 did not synergistically accelerate the EMT of HERS. Moreover, TGF-β1/FGF2-mediated EMT of HERS cells was reversed by the MEK1/2 inhibitor U0126. These results suggest that TGF-β1 and FGF2 induce the EMT of HERS through a MAPK/ERK-dependent signaling pathway. They also exert their different tendency of cellular differentiation during tooth root formation. This study further expands our knowledge of tooth root morphogenesis and provides more evidence for the use of alternative cell sources in clinical treatment of periodontal diseases.
Stem cell implantation has been utilized for the repair of spinal cord injury; however, it shows unsatisfactory performance in repairing large scale lesion of an organ. We hypothesized that dental follicle cells (DFCs), which possess multipotential capability, could reconstruct spinal cord defect (SCD) in combination with biomaterials. In the present study, mesenchymal and neurogenic lineage characteristics of human DFCs (hDFCs) were identified. Aligned electrospun PCL/PLGA material (AEM) was fabricated and it would not lead to cytotoxic reaction; furthermore, hDFCs could stretch along the oriented fibers and proliferate efficiently on AEM. Subsequently, hDFCs seeded AEM was transplanted to restore the defect in rat spinal cord. Functional observation was performed but results showed no statistical significance. The following histologic analyses proved that AEM allowed nerve fibers to pass through, and implanted hDFCs could express oligodendrogenic lineage maker Olig2 in vivo which was able to contribute to remyelination. Therefore, we concluded that hDFCs can be a candidate resource in neural regeneration. Aligned electrospun fibers can support spinal cord structure and induce cell/tissue polarity. This strategy can be considered as alternative proposals for the SCD regeneration studies.
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