Effect of GDF‐5 and BMP‐2 on the expression of tendo/ligamentogenesis‐related markers in human PDL‐derived cells

Inoue, Masakí; Ebisawa, Katsumi; Itaya, Tomotaka; Sugito, T; Yamawaki-Ogata, Aika; Sumita, Yoshinori; Wadagaki, R; Agata, Hideki; Kagami, Hideaki

doi:10.1111/j.1601-0825.2011.01871.x

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…1D-1F). Since Col2.3-GFP does not label all PDL fibroblasts, Scx-GFP was used (Inoue et al ., 2012). It was expressed at high levels in PDL fibroblasts within the cervical and periapical regions and in cells of the trans-septal ligament and at lower levels by osteocytes and cementocytes (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…Differentiation of SMA9 cells into PDL fibroblasts was confirmed in Scx-GFP mice. Scleraxis is a transcription factor, expressed in tendon progenitor populations and mature tendons as well as in PDL fibroblasts (Pryce et al ., 2007; Inoue et al ., 2012). We did not expect to detect expression of Scx-GFP in osteocytes and cementoblasts, and further studies will be required to establish whether this expression pattern is consistent with the expression of endogenous Scleraxis.…”

Section: Discussionmentioning

confidence: 99%

“…Mice in which a 2.3-kb promoter fragment of type I collagen drives GFP (Col2.3-GFP) were used to identify osteoblasts and cementoblasts (Kalajzic et al ., 2002; Braut et al ., 2003). Mice in which the Scleraxis promoter drives GFP (Scx-GFP) were utilized to identify PDL fibroblasts (Pryce et al ., 2007; Inoue et al ., 2012). αSMACreERT2 mice were crossed with Cre reporter mice (Ai9) (Madisen et al ., 2010) (Jackson Labs, Bar Harbor, ME, USA) to generate αSMACreERT2/Ai9 mice (SMA9).…”

Section: Methodsmentioning

confidence: 99%

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In vivo Identification of Periodontal Progenitor Cells

et al. 2013

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The periodontal ligament contains progenitor cells; however, their identity and differentiation potential in vivo remain poorly characterized. Previous results have suggested that periodontal tissue progenitors reside in perivascular areas. Therefore, we utilized a lineage-tracing approach to identify and track periodontal progenitor cells from the perivascular region in vivo. We used an alpha-smooth muscle actin (αSMA) promoter-driven and tamoxifen-inducible Cre system (αSMACreERT2) that, in combination with a reporter mouse line (Ai9), permanently labels a cell population, termed 'SMA9'. To trace the differentiation of SMA9-labeled cells into osteoblasts/cementoblasts, we utilized a Col2.3GFP transgene, while expression of Scleraxis-GFP was used to follow differentiation into periodontal ligament fibroblasts during normal tissue formation and remodeling following injury. In uninjured three-week-old SMA9 mice, tamoxifen labeled a small population of cells in the periodontal ligament that expanded over time, particularly in the apical region of the root. By 17 days and 7 weeks after labeling, some SMA9-labeled cells expressed markers indicating differentiation into mature lineages, including cementocytes. Following injury, SMA9 cells expanded, and differentiated into cementoblasts, osteoblasts, and periodontal ligament fibroblasts. SMA9-labeled cells represent a source of progenitors that can give rise to mature osteoblasts, cementoblasts, and fibroblasts within the periodontium.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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In vivo Identification of Periodontal Progenitor Cells

et al. 2013

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“…Picrosirius red staining and polarized light microscopy revealed collagen fiber orientation highlighted by birefringence. ScxGFP was utilized to identify the location and shape of PDL fibroblasts . To identify further the orientation of cytoskeleton and correlate it with the angular distribution of PDL fibroblasts and collagen fibers, phalloidin was employed to stain cytoplasmic actin filaments.…”

Section: Resultsmentioning

confidence: 99%

Differentiating zones at periodontal ligament–bone and periodontal ligament–cementum entheses

Lee

Schweitzer

et al. 2015

J of Periodontal Research

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Background and Objective The structural and functional integrity of bone-periodontal ligament (PDL)-cementum complex stems from the load-bearing attachment sites (entheses) between soft (PDL) and hard (bone, cementum) tissues. These attachment sites are responsible for maintenance of a bone-PDL-cementum complex biomechanical function. The objective was to investigate changes in spatiotemporal expression of key biomolecules in developing and functionally active entheses. Material and Methods Multilabeling technique was performed on hemimandibles of 3 week and 3 month-old scleraxis (scx)-GFP transgenic mice for CD146, CD31, NG2, osterix (OSX), and bone sialoprotein (BSP). Regions of dominant stretch within the PDL were evaluated by identifying directionality of collagen fibrils, PDL fibroblasts, and PDL cell cytoskeleton. Results CD146+ cells adjacent to CD31+ vasculature were identified at PDL-bone enthesis. NG2+ cells were located at coronal bone-PDL and apical cementum-PDL entheses in the 3 weeks-old group, but at 3 months, NG2 was positive at the entheses of the apical region and alveolar crest. NG2 and OSX were colocalized at the osteoid and cementoid regions of the PDL-bone and PDL-cementum entheses. BSP was prominent at the apical region of 3 week old mice. The directionality of collagen fibers, fibroblasts, and their cytoskeleton overlapped, except in the apical region of 3 weeks. Conclusion Colocalization of biomolecules at zones of the periodontal ligament adjacent to attachment sites may be essential for the formation of precementum and osteoid interfaces at a load-bearing bone-PDL-tooth fibrous joint. Biophysical cues resulting from development and function can regulate recruitment and differentiation of stem cells potentially from vascular origin toward osteo- and cemento-blastic lineages at the PDL-bone and PDL-cementum entheses. Investigating the coupled effect of biophysical and biochemical stimuli leading to cell differentiation at the functional attachment sites is critical for developing regeneration strategies to enable functional reconstruction of the periodontal complex.

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“…In both the pulp of the teeth and the periodontal ligament (PDL), the primary connective tissue attachment of the tooth roots to the bone, we found increased cell proliferation, increased HIF-1α levels, bone-PDL interactions, vascularization, and tissue specific progenitor and stem cell markers. These included 1) scleraxis, a transcription factor expressed in tendon progenitor populations and mature tendon and which has also been found in PDL fibroblasts (30)(31)(32)(33) and 2) neurofilament, a structural protein of mature nerve fibers, was seen in the pulp and also found in the PDL (34). The known pulp markers of progenitor cell populations, shown to be mesenchymal stem cells (MSC), alpha smooth muscle actin (aSMA) and CD44 (35)(36)(37)(38), were increased after drug treatment.…”

Section: Introductionmentioning

confidence: 93%

Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis

Zebrowitz

Kajikawa

Bedelbaeva

et al. 2021

Preprint

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Bone injuries and fractures reliably heal through a process of regeneration with restoration to original structure and function when the gap between adjacent sides of a fracture site is small. However, when there is significant volumetric loss of bone, bone regeneration usually does not occur.In the present studies, we explore a particular case of volumetric bone loss in a mouse model of human periodontal disease (PD) in which alveolar bone surrounding teeth is permanently lost and not replaced. This model employs the placement a ligature around the upper second molar which leads to inflammation and bone breakdown and faithfully replicates the bacterially-induced inflammatory etiology of human PD to induce bone degeneration. After 10 days, the ligature is removed and the mice are treated with a timed-release formulation of a small molecule inhibitor of prolylhydroxylases (PHDi; 1,4-DPCA) previously shown to induce epimorphic regeneration of soft tissue in non-regenerating mice. This PHDi induces high expression of HIF-1α and the regenerative response is completely blocked by siHIF1a. Here, we observe that timed-release 1,4-DPCA rapidly and completely restores bone and soft tissue with normal anatomic fidelity and with increased stem cell markers due to stem cell migration into the site and/or de-differentiation of local tissue, PDL cell proliferation, and increased vascularization. In-vitro studies using gingival tissue show that 1,4-DPCA indeed induces de-differentiation and the expression of stem cell markers but does not exclude the role of migrating stem cells.

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Effect of GDF‐5 and BMP‐2 on the expression of tendo/ligamentogenesis‐related markers in human PDL‐derived cells

Abstract: Growth differentiation factor 5 induced the expression of scleraxis and may enhance tendo/ligamentogenesis in human periodontal ligament-derived cells. The expression of scleraxis was higher in STRO-1-negative fraction, suggesting more differentiated state of the cells.

Cited by 8 publications

References 32 publications

In vivo Identification of Periodontal Progenitor Cells

In vivo Identification of Periodontal Progenitor Cells

Differentiating zones at periodontal ligament–bone and periodontal ligament–cementum entheses

Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis

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