Between a rock and a hard place: Regulation of mineralization in the periodontium

Andras, Natalie L; Mohamed, Fatma F.; Chu, Emily Y.; Foster, Brian L.

doi:10.1002/dvg.23474

Cited by 7 publications

(6 citation statements)

References 206 publications

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“…Therefore, ROCK1 mediated the regulatory role of ZEB1 in hP-DLSCs in response to LPS. It has been reported that ROCK signaling is implicated in bone metabolism, which affects the proliferation and migration of hPDLSCs, and regulates mineralization in the periodontium (Andras et al, 2022;Wang et al, 2017;Xu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, ROCK1 mediated the regulatory role of ZEB1 in hPDLSCs in response to LPS. It has been reported that ROCK signaling is implicated in bone metabolism, which affects the proliferation and migration of hPDLSCs, and regulates mineralization in the periodontium (Andras et al, 2022; Wang et al, 2017; Xu et al, 2022). Accumulating evidence has demonstrated that AMPK mediates bone loss and affects the progression of periodontitis in rats with periodontitis (Araújo et al, 2017; Díaz et al, 2020; Tamaki et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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ZEB1 interferes with human periodontal ligament stem cell proliferation and differentiation

Qian

Zhang

2023

Oral Diseases

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BackgroundPeriodontitis can eventually contribute to tooth loss. Zinc finger E‐box binding homeobox 1 (ZEB1) is identified as overexpressed in the gingival tissue of mice with periodontitis. This study is designed to decipher the mechanism of ZEB1's involvement in periodontitis.MethodsHuman periodontal mesenchymal stem cells (hPDLSCs) were exposed to LPS to mimic the inflammation in periodontitis. Following ZEB1 silencing, FX1 (an inhibitor of Bcl‐6) treatment or ROCK1 overexpression, cell viability, and apoptosis were analyzed. Alkaline phosphatase (ALP) staining, Alizarin red staining, RT‐qPCR, and western blot were performed to evaluate osteogenic differentiation and mineralization. hPDLSCs were processed for luciferase reporter assay and ChIP‐PCR to confirm the association between ZEB1 and ROCK1.ResultsThe induction of ZEB1 silencing resulted in reduced cell apoptosis, enhanced osteogenic differentiation, and mineralization. Nevertheless, these effects were significantly blunted by FX1. ZEB1 was confirmed to bind to the promoter sites of ROCK1 and regulate the ROCK1/AMPK. Whereas ROCK1 overexpression reversed the effects of ZEB1 silencing on Bcl‐6/STAT1, as well as cell proliferation and osteogenesis differentiation.ConclusionhPDLSCs displayed decreased proliferation and weakened osteogenesis differentiation in response to LPS. These impacts were mediated by ZEB1 regulating Bcl‐6/STAT1 via AMPK/ROCK1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ZEB1 interferes with human periodontal ligament stem cell proliferation and differentiation

Qian

Zhang

2023

Oral Diseases

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“…Though cementum is sensitive to disturbances in phosphate metabolism (e.g., X-linked hypophosphatemia), [103][104][105][106][107] regulators of inorganic pyrophosphate (e.g., progressive ankylosis protein [ANK] and ectonucleotide pyrophosphatase phosphodiesterase 1 [ENPP1]) exert control over cementum apposition and represent one of several lines of defense against pathological cementum expansion. [108][109][110] These collected observations point to alveolar bone as the periodontal tissue primarily targeted by CKD-MBD. We did note that increased bone resorption and formation, hyperphosphatemia, and altered ECM composition may all contribute to regions of ankylosis associated with CKD, though the respective contributions and sequence of events require further study.…”

Section: Journal Of Bone and Mineral Researchmentioning

confidence: 99%

Dentoalveolar Alterations in an Adenine‐Induced Chronic Kidney Disease Mouse Model

Mohamed,

Amadeu de Oliveira,

Kinoshita

et al. 2023

J of Bone & Mineral Res

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Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD–MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD–MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)‐induced CKD (AD–CKD) mouse model. Eight‐week‐old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high‐phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro–computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp‐dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue‐nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD–CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD‐associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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“…A better understanding of the manner in which non-collagenous macromolecules can influence mineralization may help in the design of scaffolds for recreating the critical PDL-cementum interface in periodontal regeneration. Cellular regulation of mineralization in the periodontium has recently been reviewed by Foster and colleagues (46). The key effectors include regulators of phosphate metabolism, pyrophosphate metabolism, and extracellular matrix proteins as discussed above.…”

Section: Control Of Mineralization At the Pdl-cementum Interfacementioning

confidence: 99%

Periodontal regeneration: Lessons from the periodontal ligament-cementum junction in diverse animal models

Sone

McCulloch²

2023

Front. Dent. Med

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The attachment of the roots of mammalian teeth of limited eruption to the jawbone is reliant in part on the mineralization of collagen fibrils of the periodontal ligament (PDL) at their entry into bone and cementum as Sharpey's fibers. In periodontitis, a high prevalence infection of periodontal tissues, the attachment apparatus of PDL to the tooth root is progressively destroyed. Despite the pervasiveness of periodontitis and its attendant health care costs, and regardless of decades of research into various possible treatments, reliable restoration of periodontal attachment after surgery is not achievable. Notably, treatment outcomes in animal studies have often demonstrated more positive regenerative outcomes than human clinical studies. Conceivably, defining how species diversity affects cementogenesis and cementum/PDL regeneration could be instructive for informing novel and more efficacious treatment strategies. Here we briefly review differences in cementum and PDL attachment in commonly used animal models to consider how species differences may lead to enhanced regenerative outcomes.

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Between a rock and a hard place: Regulation of mineralization in the periodontium

Cited by 7 publications

References 206 publications

ZEB1 interferes with human periodontal ligament stem cell proliferation and differentiation

ZEB1 interferes with human periodontal ligament stem cell proliferation and differentiation

Dentoalveolar Alterations in an Adenine‐Induced Chronic Kidney Disease Mouse Model

Periodontal regeneration: Lessons from the periodontal ligament-cementum junction in diverse animal models

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