Successful Periodontal Ligament Regeneration by Periodontal Progenitor Preseeding on Natural Tooth Root Surfaces

Dangaria, Smit; Ito, Yoshihiro; Diekwisch, Thomas G.H.

doi:10.1089/scd.2010.0431

Cited by 82 publications

(70 citation statements)

References 36 publications

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“…Thus, several dental diseases such as chronic periodontitis and periapical periodontitis are closely related to PDL disorders. Although PDL reconstitution has not been established, PDL regeneration should improve tooth substitution techniques (Chen and Jin, 2010;Dangaria et al, 2011). The identification of a key transcription factor regulating PDL development and homeostasis should contribute to therapeutic advancement in the dental field.…”

Section: Discussionmentioning

confidence: 99%

Mohawk transcription factor regulates homeostasis of the periodontal ligament

et al. 2016

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The periodontal ligament (PDL), which connects the teeth to the alveolar bone, is essential for periodontal tissue homeostasis. Although the significance of the PDL is recognized, molecular mechanisms underlying PDL function are not well known. We report that mohawk homeobox (Mkx), a tendon-specific transcription factor, regulates PDL homeostasis by preventing its degeneration. Mkx is expressed in the mouse PDL at the age of 10 weeks and expression remained at similar levels at 12 months. In Mkx −/− mice, agedependent expansion of the PDL at the maxillary first molar (M1) furcation area was observed. Transmission electron microscopy (TEM) revealed that Mkx −/− mice presented collagen fibril degeneration in PDL with age, while the collagen fibril diameter gradually increased in Mkx +/+ mice. PDL cells lost their shape in Mkx −/− mice, suggesting changes in PDL properties. Microarray and quantitative polymerase chain reaction (qPCR) analyses of Mkx −/− PDL revealed an increase in osteogenic gene expression and no change in PDL-and inflammatory-related gene expression. Additionally, COL1A1 and COL1A2 were upregulated in Mkxoverexpressing human PDL fibroblasts, whereas osteogenic genes were downregulated. Our results indicate that Mkx prevents PDL degeneration by regulating osteogenesis.

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Section: Discussionmentioning

confidence: 99%

Mohawk transcription factor regulates homeostasis of the periodontal ligament

et al. 2016

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“…Along with concerted efforts to produce predictable and reliable approaches to augment bone regeneration in intrabony bone defects, the development of tissue engineering and regenerative medicine has provided new avenues to improve the clinical outcomes of periodontal regeneration using stem cell-based technologies (Chen and Jin 2010;Izumi et al 2011;Chen et al 2012;Lu et al 2013;Monsarrat et al 2014). In this context, stem cells derived from the PDL (PDLSCs) have been demonstrated to be effective in preclinical trials and have been suggested as the best cell type for periodontal tissue regeneration (Iwata et al 2010;Dangaria et al 2011;Tsumanuma et al 2011;Dan et al 2014). Despite several small-scale pilot/feasibility studies that have been performed in humans (Feng et al 2010;Chen et al 2016), the clinical use of PDLSCs for periodontal regeneration still faces numerous challenges (Hynes et al 2012;Lu et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Effects of short-term inflammatory and/or hypoxic pretreatments on periodontal ligament stem cells: in vitro and in vivo studies

et al. 2016

Cell Tissue Res

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In this study, we extensively screened the in vitro and in vivo effects of PDLSCs following short-term inflammatory and/or hypoxic pretreatments. We found that the 24-h hypoxic pretreatment of PDLSCs significantly enhanced cell migration and improved cell surface CXCR4 expression. In addition, hypoxia-pretreated PDLSCs exhibited improved cell colony formation and proliferation. Cells that were dually stimulated also formed more colonies compared to untreated cells but their proliferation did not increase. Importantly, the hypoxic pretreatment of PDLSCs enhanced cell differentiation as determined by elevated RUNX-2 and ALP protein expression. In this context, the inflammatory stimulus impaired cell OCN protein expression, while dual stimuli led to decreased RUNX-2 and OCN mRNA levels. Although preconditioning PDLSCs with inflammatory and/or hypoxic pretreatments resulted in no differences in the production of matrix proteins, hypoxic pretreatment led to the generation of thicker cell sheets; the inflammatory stimulus weakened the ability of cells to form sheets. All the resultant cell sheets exhibited clear bone regeneration following ectopic transplantation as well as in periodontal defect models; the amount of new bone formed by hypoxia-preconditioned cells was significantly greater than that formed by inflammatory stimulus- or dual-stimuli-treated cells or by nonpreconditioned cells. The regeneration of new cementum and periodontal ligaments was only identified in the hypoxia-stimulus and no-stimulus cell groups. Our findings suggest that PDLSCs that undergo short-term hypoxic pretreatment show improved cellular behavior in vitro and enhanced regenerative potential in vivo. The preconditioning of PDLSCs via combined treatments or an inflammatory stimulus requires further investigation.

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“…In addition, an organ culture study performed on tooth root surfaces showed that new alveolar bone and PDLlike tissues were formed only by PDLCs, but not by MSCs, DPCs, or DFCs. 5 These results suggest that PDLCs are the most suitable cell population for periodontal regeneration.…”

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confidence: 87%

“…[2][3][4][5] Biomaterials offer tissue engineering and regenerative medicine a powerful tool in the form of cell delivery vehicles and scaffolds. A three-dimensional scaffold, serving as a space maintainer to temporarily support stem/ progenitor cell attachment, proliferation, and differentiation, is an important element for tissue engineering.…”

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confidence: 99%