Peroxisome proliferator activated receptor γ promotes mineralization and differentiation in cementoblasts via inhibiting Wnt/β‐catenin signaling pathway

Hu, Yingying; Wang, Changning; Ha, Shanshan; Zhu, Ningjing; Cao, Zhengguo; Song, Yaling

doi:10.1002/jcb.29509

Cited by 6 publications

(14 citation statements)

References 45 publications

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“…24,25 Moreover, our previous studies have demonstrated that activated WNT/β-catenin signalling and accumulation of β-catenin in the nucleus could inhibit mineralization in ameloblasts and cementoblasts. 26,28 In the present study, we found increased translocation of β-catenin into the nucleus and reduced differentiation activity in ALC-Per2-sh cells. Meanwhile, overexpression of PPARγ partially rescued the inhibited differentiation activity in ALC-Per2-sh cells, which was characterized by enhanced AKT1 and β-catenin phosphorylation levels, decreased expression of β-catenin in the nucleus and increased ALP staining and ALP activity in the ALC-Per2-sh-pEnCMV-Pparγ group.…”

Section: Discussionsupporting

confidence: 61%

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PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis

et al. 2021

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Circadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.

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Section: Discussionsupporting

confidence: 61%

“…PPARγ was reported to participate in AKT phosphorylation and β-catenin regulation. 21,27,28 Here, we found that the mandibular first molar germs of circadian disturbance mice exhibited reduced protein expression of BMAL1 (Supplemental Fig. S2a), PER2, PPARγ and AMELX (Fig.…”

Section: Resultsmentioning

confidence: 67%

PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis

et al. 2021

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“…The markers of macrophages have also been shown to diversely affect cementoblast mineralization. The M1 polarization markers IL-1β, IL-6, and TNF-α were observed to attenuate the mineralization of cementoblasts, while the M2 polarization marker PPARγ was suggested to be a promoter of cementoblast mineralization [14][15][16][17]. In the present study, we examined the effect of macrophages with different polar-ization phenotypes on the mineralization of cementoblasts.…”

Section: Discussionmentioning

confidence: 91%

“…On that basis, Li et al conducted in vitro experiments to demonstrate that M2-polarized macrophages could enhance the cementoblastic differentiation of periodontal ligament stem cells [13]. Further explorative experiments found that the M1 polarization markers IL-1β, IL-6, and TNF-α could attenuate the mineralization of cementoblasts, while the M2 polarization marker PPARγ promoted cementoblast mineralization [14][15][16][17]. These results all suggested a potential linkage between macrophages, cementoblasts, and root resorption.…”

Section: Introductionmentioning

confidence: 99%

Macrophages with Different Polarization Phenotypes Influence Cementoblast Mineralization through Exosomes

Zhao

Huang

Líu

et al. 2022

Stem Cells International

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Root resorption is a common dental challenge that can lead to tooth loosening or even tooth loss. Among the cells involved in root resorption, cementoblasts are responsible for laying down the cementum, while macrophages with different phenotypes have also been shown to have bidirectional effects on root resorption. However, the relationship between macrophages and cementoblasts remains largely unknown. In this study, we examined the effect of macrophages with different polarization phenotypes on the mineralization of cementoblasts. Using the transwell coculture system and a conditioned medium-based coculture system, we found that compared with M0 (unpolarized macrophages), M1-polarized macrophages attenuated cementoblast mineralization, while M2-polarized macrophages enhanced cementoblast mineralization. Furthermore, by extracting M0/M1/M2 macrophage exosomes and examining their effects on the mineralization of cementoblasts, we found that the effects of macrophages on cementoblast mineralization were, at least partially, exerted by exosomes. Moreover, in vivo studies also indicated that an increased M1/M2 ratio could suppress cementoblast mineralization and bring about root resorption. During mechanical forceinduced orthodontic tooth movement (OTM), root resorption was evident on the compression side of periodontal tissue, and a higher M1/M2 ratio and weaker cementoblast mineralization were observed on the compression side than on the tension side. We also used localized lipopolysaccharide (LPS) injection to increase the M1/M2 ratio around the roots of maxillary molars, where root resorption and decreased cementoblast mineralization were also observed. Furthermore, when we injected the exosomes from M0 and M1-and M2-polarized macrophages into mice, it was observed that the cementoblast mineralization was attenuated in the group injected with M1-polarized macrophage exosomes, while it was augmented in the group injected with M2-polarized macrophage exosomes.

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“…Wnt signaling is putatively involved in various developmental processes such as skeletal development and tooth formation (Hu et al, 2019;Wang et al, 2019). It has been shown in various report that canonical Wnt signaling is activated during osteogenic differentiation in human bone marrow mesenchymal stem cells (BMMSCs) (Matsushita et al, 2020;Xiang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Epithelial Cell Rests of Malassez Provide a Favorable Microenvironment for Ameliorating the Impaired Osteogenic Potential of Human Periodontal Ligament Stem Cells

Liu

Zhang

et al. 2021

Front. Physiol.

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Human periodontal ligament stromal/stem cells (PDLSCs) are ideal candidates for periodontal regeneration and are of significant importance in clinical practice. However, PDLSCs derived from diseased microenvironments exert impaired behavior, which leads to the failure of periodontal regeneration. The epithelial cell rests of Malassez (ERM), which are involved in periodontal homeostasis, are residual cells from Hertwig's epithelial root sheath (HERS). However, the function of ERM remains largely unknown. Therefore, the aim of this study was to evaluate the effect of ERM on the osteogenic potential of PDLSCs from an impaired microenvironment. PDLSCs from healthy donors (H-PDLSCs), periodontitis donors (P-PDLSCs) and human ERM were harvested. Osteogenic evaluation showed a lower osteogenic potential of P-PDLSCs compared to that of H-PDLSCs. Then, we co-cultured ERM with P-PDLSCs, and the data showed that ERM promoted the expression of osteogenic genes and proteins in P-PDLSCs. In addition, we collected the PDLSCs from aged donors (A-PDLSCs) and analyzed the osteogenesis capacity of the A-PDLSCs and A-PDLSCs + ERM groups, which displayed similar results to P-PDLSCs. Finally, we evaluated the Wnt pathway, which is associated with osteogenic differentiation of stromal/stem cells, in A-PDLSCs + ERM and P-PDLSCs + ERM groups, which indicated that suppression of the Wnt pathway may result in an increase in the osteogenic properties of A-PDLSCs + ERM and P-PDLSCs + ERM groups. Taken together, the above findings shed new light on the function of ERM and provide a novel therapeutic for optimizing PDLSCs-based periodontal regeneration.

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Peroxisome proliferator activated receptor γ promotes mineralization and differentiation in cementoblasts via inhibiting Wnt/β‐catenin signaling pathway

Cited by 6 publications

References 45 publications

PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis

PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis

Macrophages with Different Polarization Phenotypes Influence Cementoblast Mineralization through Exosomes

Epithelial Cell Rests of Malassez Provide a Favorable Microenvironment for Ameliorating the Impaired Osteogenic Potential of Human Periodontal Ligament Stem Cells

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