RESUMO
The potential of stem cells, for example upper periodontal ligament stem cells from the maxilla (u-PDLSC) and from the mandible (l-PDLSC), adipose-derived mesenchymal stem cells (AD-MSC), and bone marrow-derived mesenchymal stem cells (BM-MSC), with respect to periodontal remodeling and orthodontic treatment is of great importance. In this work, we focus on the comprehensive adaptability of different stem cell types to mechanical forces with the aim to better understanding cell behavior and to refine a new mechanistic approach to investigate periodontal remodeling. We comprehensively analyze stem cells and observe distinct morphological and proliferation changes under compression in dependence on stem cell type. The cell signaling of extracellular signal-regulated kinase (ERK) and protein kinase B, also called AKT, and their respective phosphorylation shows diverse responses to compression. Additionally, vascular endothelial growth factor and hepatocyte growth factor secretion were reduced under mechanical stress in all cell types, with cell-specific variations. Osteoprotegerin secretion was reduced under compression, particularly in u-PDLSC. At least, diverse soluble receptors of NF-kB-ligand secretion patterns among cell types under pressure were observed, providing crucial insights into bone metabolism. These findings offer a deeper understanding of the behavior of mesenchymal stem cells under mechanical stimuli, highlighting their roles in bone remodeling, wound healing, and tissue regeneration in orthodontic and regenerative medicine contexts. Our results underscore the potential of u-PDLSC, l-PDLSC, and AD-MSC in periodontal regeneration, with AD-MSC showing notable resilience under compression, indicating its promising role for further investigation for orthodontic research. While these findings are encouraging, further research is essential to fully comprehend the mechanism of stem cell-based periodontal therapies.
RESUMO
BACKGROUND: Teeth and supporting oral tissues are attractive and accessible sources of stem cells. Periodontal ligament stem cells (PDLSC) are readily isolated from extracted third molars, and exhibit the ability to self-renew and differentiate into multiple mesodermal cell fates. Clinical experience suggests that the exact location of periodontal defects affects the oral bone remodeling and wound healing. Compared to the mandible, the maxilla heals quicker and more efficiently. Angiogenesis is key in tissue regeneration including dental tissues, yet few studies focus on the angiogenic potential of PDLSC, none of which considered the differences between upper and lower jaw PDLSC (u-PDLSC and l-PDLSC, respectively). METHODS: Here we studied the angiogenic potential of u-PDLSC and l-PDLSC and compared the results to well-established mesenchymal stem cells (MSC). Cells were characterized in terms of surface markers, proliferation, and vascular endothelial growth factor (VEGF) secretion, and angiogenic assays were performed. Newly formed capillaries were stained with CD31, and their expression of platelet endothelial cell adhesion molecule (PECAM-1), angiopoietin 2 (ANGPT2), and vascular endothelial growth factor receptor 1 and 2 (VEGFR-1, VEGFR-2) were measured. RESULTS: Periodontal stem cells from the upper jaw showed a higher proliferation capacity, secreted more VEGF, and formed capillary networks faster and denser than l-PDLSC. Gene expression of angiogenesis-related genes was significantly higher in u-PDLSC than in l-PDLSC or MSC, given that culture conditions were suitable. CONCLUSION: The oral cavity is a valuable source of stem cells, particularly PDLSC, which are promising for oral tissue engineering due to their robust growth, lifelong accessibility, low immunogenicity, and strong differentiation potential. Notably, u-PDLSC exhibit higher VEGF secretion and accelerate capillary formation compared to l-PDLSC or MSC. This study suggests a potential molecular mechanism in capillary formation, emphasizing the significance of precise location isolation of PDLSC.
Assuntos
Neovascularização Fisiológica , Ligamento Periodontal , Fator A de Crescimento do Endotélio Vascular , Humanos , Projetos Piloto , Ligamento Periodontal/citologia , Ligamento Periodontal/irrigação sanguínea , Neovascularização Fisiológica/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise , Células-Tronco Mesenquimais , Maxila , Mandíbula , Proliferação de Células , Células-Tronco/fisiologia , Masculino , Diferenciação Celular , Adulto , Feminino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Células Cultivadas , Adulto JovemRESUMO
One of the major components in cementum extracellular matrix is bone sialoprotein (BSP). BSP knockout (Ibsp) mice were reported to have a nonfunctional hypo-mineralized cementum, as well as detachment and disorganization of the periodontal ligament tissue. However, studies investigating the influence of Ibsp in cementoblasts are missing yet. This study investigates the influences of Bsp in three cementoblasts cell lines (OCCM.30-WT,IbspΔNterm, and IbspKAE). The mRNA expression of cementoblast and osteoclast markers (Col1a1, Alpl, Ocn, Runx2, Ctsk, Rankl and Opg) and the cell morphology were compared. Additionally, a functional monocyte adhesion assay was performed. To understand the influence of external stimuli, the effect of Ibsp was investigated under static compressive force, mimicking the compression side of orthodontic tooth movement. Cementoblasts with genotype IbspΔNterm and IbspKAE showed slight differences in cell morphology compared to OCCM.30-WT, as well as different gene expression. Under compressive force, the Ibsp cell lines presented expression pattern markers similar to the OCCM.30-WT cell line. However, Cathepsin K was strongly upregulated in IbspΔNterm cementoblasts under compressive force. This study provides insight into the role of BSP in cementoblasts and explores the influence of BSP on periodontal ligament tissues. BSP markers in cementoblasts seem to be involved in the regulation of cementum organization as an important factor for a functional periodontium. In summary, our findings provide a basis for investigations regarding molecular biology interactions of BSP in cementoblasts, and a supporting input for understanding the periodontal and cellular cementum remodeling.