Wnt signaling regulates homeostasis of the periodontal ligament

Lim, Won Hee; Liu, B.; Cheng, Du; Williams, Bart O.; Mah, Su-Jung; Helms, Jill A.

doi:10.1111/jre.12158

Cited by 76 publications

(70 citation statements)

References 57 publications

(75 reference statements)

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“…It is not clear if β-catenin is responsible for bone maintenance in response to loading, plays a role in mechanotransduction in alveolar bone around teeth, or plays a role in the functions of the PDL. Supporting evidence shows β-catenin expression in the PDL in mice (Lim et al, 2014, Premaraj et al, 2011) in addition to being present in osteocytes and cementocytes. A recent study using PDL stem cells showed that β-catenin could regulate osteogenic differentiation in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway, which is similar to the regulation by β-catenin of bone homeostasis (Liu et al, 2011).…”

Section: Role Of β-Catenin Signaling In the Periodontal Ligament (mentioning

confidence: 90%

“…A recent study using PDL stem cells showed that β-catenin could regulate osteogenic differentiation in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway, which is similar to the regulation by β-catenin of bone homeostasis (Liu et al, 2011). With the osteocalcin-Cre; Wntless fl/fl mice (Wntless, a conserved membrane protein gene dedicated to the secretion of Wnt proteins), a pathological widening of the periodontal ligament space is observed with this elimination of Wntless in teeth (Lim, Liu, 2014). An in vivo study using human PDL cells showed responses to the activation of β-catenin via LiCl, leading to intensive β-catenin nuclear translocation (Premaraj, Souza, 2011).…”

Section: Role Of β-Catenin Signaling In the Periodontal Ligament (mentioning

confidence: 99%

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The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth

Duan

Bonewald

2016

The International Journal of Biochemistry & Cell Biology

286

221

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The Wnt signaling pathway is known as one of the important molecular cascades that regulate cell fate throughout lifespan. The Wnt signaling pathway is further separated into the canonical signaling pathway that depends on the function of β-catenin (Wnt/β-catenin pathway) and the noncanonical pathways that operate independently of β-catenin (planar cell polarity pathway and Wnt/Ca2+ pathway). The Wnt/β-catenin signaling pathway is complex and consists of numerous receptors, inhibitors, activators, modulators, phosphatases, kinases and other components. However, there is one central, critical molecule to this pathway, β-catenin. While there are at least 3 receptors, LRP 4, 5 and 6, and over twenty activators known as the wnts, and several inhibitors such as sclerostin, dickkopf and secreted frizzled-related protein, these all target β-catenin. These regulators/modulators function to target β-catenin either to the proteasome for degradation or to the nucleus to regulate gene expression. Therefore, the interaction of β-catenin with different factors and Wnt/β-catenin signaling pathway will be the subject of this review with a focus on how this pathway relates to and functions in the formation and maintenance of bone and teeth based on mainly basic and pre-clinical research. Also in this review, the role of this pathway in osteocytes, bone cells embedded in the mineralized matrix, is covered in depth. This pathway is not only important in mineralized tissue growth and development, but for modulation of the skeleton in response to loading and unloading and the viability and health of the adult and aging skeleton.

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Section: Role Of β-Catenin Signaling In the Periodontal Ligament (mentioning

confidence: 90%

Section: Role Of β-Catenin Signaling In the Periodontal Ligament (mentioning

confidence: 99%

The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth

Duan

Bonewald

2016

The International Journal of Biochemistry & Cell Biology

286

221

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“…Osteocalcin-Cre (OC-Cre) mice were generated with 1.3-kb mouse osteocalcin promoter as described previously (Tan et al 2007). This promoter is different from the OCN-Cre generated with human Osteocalcin promoter (10 kb; Zhang et al 2002) used by Lim et al (2014aLim et al ( , 2014bLim et al ( , 2014c CO/CO mice. The offspring were genotyped by polymerase chain reaction (PCR) analysis using previously described primers (Tan et al 2007;Carpenter et al 2010).…”

Section: Mouse Strainsmentioning

confidence: 99%

Wntless Regulates Dentin Apposition and Root Elongation in the Mandibular Molar

Bae

Kim

et al. 2015

J Dent Res

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Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. However, it remains unclear if Wnt ligands, produced from dental mesenchyme, are necessary for odontoblast differentiation and dentin formation. Here, we show that odontoblast-specific disruption of Wntless (Wls), a chaperon protein that regulates Wnt sorting and secretion, leads to severe defects in dentin formation and root elongation. Dentin thickness decreased remarkably and pulp chambers enlarged in the mandibular molars of OC-Cre;Wls CO/CO mice. Although the initial odontoblast differentiation was normal in the mutant crown, odontoblasts became cuboidal and dentin thickness was reduced. In immunohistochemistry, Wnt10a, β-catenin, type I collagen, and dentin sialoprotein were significantly down-regulated in the odontoblasts of mutant crown. In addition, roots were short and root canals were widened. Cell proliferation was reduced in the developing root apex of mutant molars. Furthermore, Wnt10a and Axin2 expression was remarkably decreased in the odontoblasts of mutant roots. Deletion of the Wls gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation and root elongation.

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“…The removal of Wnt-β-catenin signal in the periodontium leads to severe defects in the PDL and alveolar bone formation (11). In contrast, enhancing Wnt-β-catenin signal activity by removing its antagonist, sclerostin (the product of the Sost gene), results in an increase in alveolar bone volume and reduced PDL width (12).…”

Section: Introductionmentioning

confidence: 99%

Critical roles of periostin in the process of orthodontic tooth movement

Rangiani

Jing

Ren

et al. 2015

EORTHO

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These authors contributed equally to this paper. SummaryAim: The process of orthodontic tooth movement (OTM) involves multiple mechanisms of action including bone and extracellular matrix remodelling, although the role of periodontal ligament (PDL) in this process is largely unknown. Periostin, which is highly expressed in the PDL, is known to be responsible for mechanical stimulation in maintaining the integrity of periodontal tissues. We hypothesize that this protein plays an important role during OTM. Material and methods: By using spring in 4-week-old wild-type (WT) and periostin null mice, the rate of tooth movement and mineralization were evaluated. For the evaluation, double labelling, expression of sclerostin (SOST), number of TRAP-positive cells, and quality of collagen fibrils by Sirius red were analysed and compared between these two groups. Results: Our findings showed that the distance of the tooth movement and mineral deposition rates were significantly reduced in periostin null mice (P < 0.05), with a lack of expression changes in SOST as observed in the WT group. The arrangement, digestion, and integrity of collagen fibrils were impaired in periostin null mice. The number of osteoclasts reflected by expressions of TRAP (tartrateresistant acid phosphatase) in the null mice was also significantly lower than the WT control (P < 0.05). Conclusion: Periostin plays a stimulatory role in both SOST and TRAP responses to OTM in the compassion site, although it is not clear if this role is direct or indirect during orthodontic loading.

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Wnt signaling regulates homeostasis of the periodontal ligament

Cited by 76 publications

References 57 publications

The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth

The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth

Wntless Regulates Dentin Apposition and Root Elongation in the Mandibular Molar

Critical roles of periostin in the process of orthodontic tooth movement

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