Cementoblasts, tooth root lining cells, are responsible for laying down cementum on the root surface, a process that is indispensable for establishing a functional periodontal ligament. Cementoblasts share phenotypical features with osteoblasts. Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions; however the role of Wnt signaling on cementogenesis has not been examined. In this study, we have identified a consistent expression profile of Wnt signaling molecules in cementoblasts, in vitro by RT-PCR. Exposure of cells to LiCl, which promotes canonical Wnt signaling by inhibiting GSK-3beta, increased beta-catenin nuclear translocation and up-regulated the transcriptional activity of a canonical Wnt-responsive promoters, suggesting that an endogenous canonical Wnt pathway functions in cementoblasts. Activation of endogenous canonical Wnt signaling with LiCl suppressed alkaline phosphatase (ALP) activity and expression of genes associated with cementum function; ALP, bone sialoprotein (BSP), and osteocalcin (OCN). Exposure to Wnt3a, as a representative canonical Wnt member, also inhibited the expression of ALP, BSP, and OCN gene. This effect was accompanied by decreased gene expression of Runx2 and Osterix and by increased gene expression of lymphoid enhancer factor-1. Pretreatment with Dickkopf (Dkk)-1, a potent canonical Wnt antagonist, which binds to a low-density lipoprotein-receptor-related protein (LRP)-5/6 co-receptor, attenuated the suppressive effects of Wnt3a on mRNA expression of Runx2 and OCN on cementoblasts. These findings suggest that canonical Wnt signaling inhibits cementoblast differentiation via regulation of expression of selective transcription factors. Wnt3a also increased the expression of cyclin D1, known as a cell cycle regulator, as well as cell proliferation. In conclusion, these observations suggest that Wnt signaling inhibits cementoblast differentiation and promotes cell proliferation. Elucidating the role of Wnt in controlling cementoblast function will provide new tools needed to improve on existing periodontal regeneration therapies.
"The pattern of Wnt responding cells in the periodontium has been mapped (Rooker et al. 2010; Lim, Liu, Cheng, Williams, et al. 2014): X-gal +ve cells populate the periodontal ligament space and decorate the surfaces of the alveolar bone (Fig. 2B). Cementoblasts covering the dentin surface are also Wnt responsive, as shown by GFP immunostaining in tissue sections from Axin2 CreERT2/+ ;R26 mTmG/+ mice (Fig. 2C, D and see Nemoto et al. 2009). From these data, one can assume that endogenous Wnt signaling is active in the adult periodontium. "
"Recent studies in vivo have reported that constitutive stabilization of βcatenin in dental mesenchyme leads to excessive cementum formation [14,15], and that disruption of Wnt/β-catenin signaling in dental mesenchyme arrests the differentiation of cementoblasts , suggesting that canonical Wnt/β-catenin signaling is required for cementum formation. In addition, studies in vitro have demonstrated that Wnt/β-catenin signaling up-regulates differentiation and proliferation in rat/mouse dental follicle cells   and murine cementoblasts , respectively, suggesting the involvement of Wnt/β-catenin signaling in cementogenesis. "
"Sr, activating the ERK1/2 pathway, favored the phosphorylation of PPARγ and its degradation, thereby explaining the significant decrease of PPARγ2 protein observed under Sr treatment and the less dramatic inhibition of the PPARγ2 gene expression. Cyclin D1 is an important cell cycle regulator, promoting proliferation in cell types including epithelial cells, cementoblasts and human MMCs    via an ERK1/2 signaling pathway . Moreover, in fibroblasts cultured in adipogenic medium, Fu M. et al. (2005)  demonstrated that cyclin D1 inhibits the PPARγ activity by inducing a histone deacetylase (HDAC) activity that favors a transcriptionally inactive chromatin. "
[Show abstract][Hide abstract] ABSTRACT: Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later on. We hypothesized that the quality of the dietary protein is of prime importance for bone physiology during moderate protein restriction. The target population was growing Balb/C mice. We compared two protein restricted diets (6% of total energy as protein), one based on soy (LP-SOY) and one based on casein (LP-CAS). For comparison, a normal protein soy-based control group (NP-SOY) and a low protein group receiving an anabolic daily parathyroid hormone (PTH) 1-34 injection (LP-SOY + PTH) were included in the protocol. After 8 weeks, LP-SOY mice had reduced body weights related to a lower lean mass whereas LP-CAS mice were not different from the NP-SOY group. LP-SOY mice were characterized by lower femoral cortical thickness, bone volume, trabecular number and thickness and increased medullar adiposity when compared to both the LP-CAS and NP-SOY groups. However, the dietary intervention had no effect on the vertebral parameters. The negative effect of the LP-SOY diet was correlated to an impaired bone formation as shown by the reduced P1NP serum level as well as the reduced osteoid surfaces and bone formation rate in the femur. PTH injection in LP-SOY mice had no effect on total weight or lean mass, but improved all bone parameters at both femoral and vertebral sites, suggesting that amino acid deficiency was not the primary reason for degraded bone status in mice consuming soy protein. In conclusion, our study showed that under the same protein restriction (6% of energy), a soy diet leads to impaired bone health whereas a casein diet has little effect when compared to a normal protein control.
Bone 02/2014; 59:7–13. DOI:10.1016/j.bone.2013.10.013 · 3.97 Impact Factor
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