Stem cell properties of Gli1-positive cells in the periodontal ligament

Hosoya, Akihiro; Shalehin, Nazmus; Takebe, Hiroaki; Fujii, Shohei; Seki, Yuri; Mizoguchi, Takahiro; Shimo, Tsuyoshi; Iijima, Masahiro; Irie, Kazuharu

doi:10.1016/j.job.2020.08.002

Cited by 23 publications

(19 citation statements)

References 63 publications

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“…Nevertheless, Gli1-Cre ERT2 was not only activated in PDL cells but also in cells from bone marrow, as shown from cell lineage tracing date in the present study and previous studies (Feng et al, 2017;Hosoya et al, 2020;Yi et al, 2021). To date, no specific markers could be used to discern differences between PDLderived and bone-marrow-derived Gli1 Lin cells.…”

Section: Discussionsupporting

confidence: 76%

“…Given the limitations of non-inducible Cre transgenic mice in early studies and differing results from different studies, we intended to assess the postnatal effects of TGFβ signaling in alveolar bone development using inducible Cre mouse lines. Specifically, we included Gli1 (a marker for mesenchymal progenitor cells in various tissues including PDL and alveolar bone) to target the early progenitor cells (Kitaura et al, 2014;Feng et al, 2017;Shi et al, 2017;Hosoya et al, 2020;Liu et al, 2020;Men et al, 2020;Yi et al, 2021); 3.2 kb Col1 was used to target osteoblasts (Rossert et al, 1995;Qin et al, 2019). Our findings revealed a key role in TGFβ signaling during early postnatal alveolar bone development.…”

Section: Introductionmentioning

confidence: 92%

“…On the other hand, we have recently begun to gain knowledge on a third type of ossification process within alveolar bone, which holds teeth. Cell lineage tracing studies showed that periodontal ligament (PDL) progenitor cells contribute to alveolar bone formation and regeneration (Ren et al, 2015;Hosoya et al, 2020;Men et al, 2020). This occurrence is distinct from that of other cell sources such as periosteum for the mandible body or chondrocytes for the mandible ramus (Hinton et al, 2015(Hinton et al, , 2017Jing et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

Xie

Zhao

et al. 2021

Front. Physiol.

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Transforming growth factor beta (TGFβ) signaling plays an important role during osteogenesis. However, most research in this area focuses on cortical and trabecular bone, whereas alveolar bone is largely overlooked. To address the role of TGFβR2 (the key receptor for TGFβ signaling) during postnatal alveolar bone development, we conditionally deleted Tgfβr2 in early mesenchymal progenitors by crossing Gli1-CreERT2; Tgfβr2flox/flox; R26RtdTomato mice (named early cKO) or in osteoblasts by crossing 3.2kb Col1-CreERT2; Tgfβr2flox/flox; R26RtdTomato mice (named late cKO). Both cKO lines were induced at postnatal day 5 (P5) and mice were harvested at P28. Compared to the control littermates, early cKO mice exhibited significant reduction in alveolar bone mass and bone mineral density, with drastic defects in the periodontal ligament (PDL); conversely, the late cKO mice displayed very minor changes in alveolar bone. Mechanism studies showed a significant reduction in PCNA+ PDL cell numbers and OSX+ alveolar bone cell numbers, as well as disorganized PDL fibers with a great reduction in periostin (the most abundant extracellular matrix protein) on both mRNA and protein levels. We also showed a drastic reduction in β-catenin in the early cKO PDL and a great increase in SOST (a potent inhibitor of Wnt signaling). Based on these findings, we conclude that TGFβ signaling plays critical roles during early alveolar bone formation via the promotion of PDL mesenchymal progenitor proliferation and differentiation mechanisms.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

Xie

Zhao

et al. 2021

Front. Physiol.

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“…Meniscus is somewhat similar to periodontal ligament (PDL) and enthesis in skeleton. Prior studies have shown that Gli1 + PDL cells contribute to the formation of periodontal tissues and can regenerate alveolar bone ( Hosoya et al, 2020 ). Many studies also demonstrated the importance of Gli1 lineage cells as the progenitors in the development and regeneration of enthesis ( Dyment et al, 2015 ; Schwartz et al, 2017 ; Felsenthal et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair

Wei

Sun

Gui

et al. 2021

eLife

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Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

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“…Dental MSCs share characteristics similar to bone marrow-derived MSCs in terms of proliferative capacity, cell markers, and differentiation capability into plural lineages, such as osteoblasts, chondrocytes, and adipocytes (9). Sonic hedgehog (Shh) signaling plays crucial roles in the development of numerous organs, and Gli1 + cells are co-localized with LRCs during molar tooth development (10,11). Even BrdU labeling in the stem cells becomes sparse if these LRCs continuously provide transit-amplifying cells (5,7,8).…”

Section: Introductionmentioning

confidence: 99%

The Sonic Hedgehog–Patched–Gli Signaling Pathway Maintains Dental Epithelial and Pulp Stem/Progenitor Cells and Regulates the Function of Odontoblasts

et al. 2021

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This study aimed to elucidate the role of the Sonic hedgehog (Shh)–Patched (Ptch)–Gli signaling pathway in maintaining dental epithelial and pulp stem/progenitor cells and regulating the function of odontoblasts. Doxycycline (dox)-inducible histone 2B (H2B)–green fluorescent protein (GFP) transgenic mice ingested dox at prenatal embryonic days 14.5 or 15.5 and their offspring were collected from postnatal day 1 (P1) to week 3 (P3W). Immunohistochemistry for Gli1, Ptch1, and Ptch2 and in situ hybridization for Shh and Ptch1 were conducted. Mandibular incisors of postnatal day 2 H2B-GFP transgenic and wild-type mice were cultivated in a nutrient medium with Shh antibody for 4 days and subsequently processed for immunohistochemistry for Sox2. In molars, dense H2B-GFP-label-retaining cells (H2B-GFP-LRCs) were densely distributed throughout the dental pulp during P1 to postnatal week 2 (P2W) and decreased in number by postnatal P3W, whereas the number of dense H2B-GFP-LRCs in the subodontoblastic layer increased in number at P2W. Gli1+ and Pthc1+ cells were distributed throughout the enamel organ and dental pulp, including the odontoblast and subodontoblastic layers. Shh mRNA was expressed in the inner enamel epithelium and shifted into odontoblasts after dentin deposition. Ptch1 mRNA was expressed in the inner enamel epithelium and cuspal pulpal tissue on P1 and decreased in intensity from postnatal week 1 to P3W. In incisors, the apical bud contained H2B-GFP-LRCs, Gli1+ cells, and Ptch1+ cells. The addition of Shh antibody to explants induced a decrease in the number of Sox2+ cells due to the increase in apoptotic cells in the apical bud. Thus, the Shh–Ptch–Gli signaling pathway plays a role in maintaining quiescent adult stem cells and regulating the function of odontoblasts.

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Stem cell properties of Gli1-positive cells in the periodontal ligament

Cited by 23 publications

References 63 publications

TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation

The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair

The Sonic Hedgehog–Patched–Gli Signaling Pathway Maintains Dental Epithelial and Pulp Stem/Progenitor Cells and Regulates the Function of Odontoblasts

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