Mechanical loading activates β-catenin signaling in periodontal ligament cells

Premaraj, Sundaralingam; Souza, Isabela; Premaraj, Thyagaseely Sheela

doi:10.2319/090310-519.1

Cited by 34 publications

(32 citation statements)

References 27 publications

(38 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: 89%

“…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). With loading on the human PDL cell, the activation of β-catenin was increased and inhibition of FAK suppressed β-catenin, suggesting that β-catenin mediated mechanotransduction in PDL (Premaraj et al, 2013).…”

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

277

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: 89%

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

277

221

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“…This was a transient response because after the recovery period post-load, β-catenin was localised to the cytoplasm only. This is the first report of the mechano-responsiveness of β-catenin in chondrocytes, although mechanical activation of β-catenin signalling has been reported in the colon of APC 1638N/+ mice [26], mesenchymal stem cells [27] and periodontal ligament cells [28]. In contrast to the Wnt3A stimulated cells, where β-catenin is almost completely nuclear, an additive effect of load and Wnt3A on β-catenin localisation was observed with extensive β-catenin detected in the nucleus and throughout the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis

et al. 2011

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IntroductionArticular cartilage functions in withstanding mechanical loads and provides a lubricating surface for frictionless movement of joints. Osteoarthritis, characterised by cartilage degeneration, develops due to the progressive erosion of structural integrity and eventual loss of functional performance. Osteoarthritis is a multi-factorial disorder; two important risk factors are abnormal mechanical load and genetic predisposition. A single nucleotide polymorphism analysis demonstrated an association of hip osteoarthritis with an Arg324Gly substitution mutation in FrzB, a Wnt antagonist. The purpose of this study was two-fold: to assess whether mechanical stimulation modulates β-catenin signalling and catabolic gene expression in articular chondrocytes, and further to investigate whether there is an interplay of mechanical load and Wnt signalling in mediating a catabolic response.MethodsChondrocytes were pre-stimulated with recombinant Wnt3A for 24 hours prior to the application of tensile strain (7.5%, 1 Hz) for 30 minutes. Activation of Wnt signalling, via β-catenin nuclear translocation and downstream effects including the transcriptional activation of c-jun, c-fos and Lef1, markers of chondrocyte phenotype (type II collagen (col2a1), aggrecan (acan), SOX9) and catabolic genes (MMP3, MMP13, ADAMTS-4, ADAMTS-5) were assessed.ResultsPhysiological tensile strain induced col2a1, acan and SOX9 transcription. Load-induced acan and SOX9 expression were repressed in the presence of Wnt3A. Load induced partial β-catenin nuclear translocation; there was an additive effect of load and Wnt3A on β-catenin distribution, with both extensive localisation in the nucleus and cytoplasm. Immediate early response (c-jun) and catabolic genes (MMP3, ADAMTS-4) were up-regulated in Wnt3A stimulated chondrocytes. With load and Wnt3A there was an additive up-regulation of c-fos, MMP3 and ADAMTS-4 transcription, whereas there was a synergistic interplay on c-jun, Lef1 and ADAMTS-5 transcription.ConclusionOur data suggest that load and Wnt, in combination, can repress transcription of chondrocyte matrix genes, whilst enhancing expression of catabolic mediators. Future studies will investigate the respective roles of abnormal loading and genetic predisposition in mediating cartilage degeneration.

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“…Wnt signalling is an important signalling cascade in myogenesis, regulating proliferation and satellite cell fate (reviewed in 145 ). In periodontal ligament cells (PDL), compressive stress leads to the activation of Wnt/B-catenin signalling pathway 146 , similar to in vivo compression of murine osteoblasts 147 . Exposing murine osteoblasts to shear flow upregulates Wnt pathways associated genes 148 , whereas exposing several colon cancer cell lines to shear flow inhibits Wnt/B-catenin activity 149 .…”

Section: Mechanical Loads -Stretch and Shear Forcesmentioning

confidence: 99%