Parathyroid hormone increases alveolar bone homoeostasis during orthodontic tooth movement in rats with periodontitis via crosstalk between STAT3 and β-catenin

Cheng Zhang, Tiancheng Li, Chenchen Zhou, Li Huang, Yuyu Li, Han Wang, Peipei Duan, Shujuan Zou, Li Mei, Cheng Zhang, Tiancheng Li, Chenchen Zhou, Li Huang, Yuyu Li, Han Wang, Peipei Duan, Shujuan Zou, Li Mei

Abstract

Periodontitis patients are at risk of alveolar bone loss during orthodontic treatment. The aim of this study was to investigate whether intermittent parathyroid hormone (1-34) treatment (iPTH) could reduce alveolar bone loss during orthodontic tooth movement (OTM) in individuals with periodontitis and the underlying mechanism. A rat model of OTM in the context of periodontitis was established and alveolar bone loss was observed. The control, iPTH and iPTH + stattic groups received injections of vehicle, PTH and vehicle, or PTH and the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic, respectively. iPTH prevented alveolar bone loss by enhancing osteogenesis and suppressing bone resorption in the alveolar bone during OTM in rats with periodontitis. This effect of iPTH was along with STAT3 activation and reduced by a local injection of stattic. iPTH promoted osteoblastic differentiation and might further regulate the Wnt/β-catenin pathway in a STAT3-dependent manner. The findings of this study suggest that iPTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/β-catenin crosstalk.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Micro-CT showed that OTM + PD caused increased alveolar bone loss. a A flowchart of the in vivo study Part I. b Methods for measuring the CEJ-ABC distance. c ROI for trabecular morphometry analysis. d Buccal images of specimens showing the vertical bone height in the blank, PD and OTM + PD groups and quantitative analysis of the CEJ-ABC distance. e, f BV/TV, Tb. N, Tb. Th, Tb. Sp and BMD in each group at days 7 and 14, respectively. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000 1 by one-way ANOVA with Tukey’s post hoc test
Fig. 2
Fig. 2
Daily systemic injection of PTH ameliorated alveolar bone loss in the OTM + PD group, which could be reversed by local stattic injection. a A flowchart of the in vivo study Part II. b Buccal images of specimens showing the vertical bone height in the OTM + PD, OTM + PD + PTH and OTM + PD + PTH + S groups, and quantitative analysis of the CEJ-ABC distance. c, d BV/TV, Tb. N, Tb. Th, Tb. Sp and BMD in each group at days 7 and 14, respectively. *P < 0.05, **P < 0.01, ***P < 0.001 by one-way ANOVA with Tukey’s post hoc test
Fig. 3
Fig. 3
Daily systemic injection of PTH activated STAT3 in the alveolar bone, which could be reversed by local stattic injection. Representative images of immunohistochemical staining of STAT3 (a) and p-STAT3 (Tyr705) (b) in the OTM + PD, OTM + PD + PTH and OTM + PD + PTH + S groups, and relative quantitative analysis at days 7 and 14. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000 1 by one-way ANOVA with Tukey’s post hoc test
Fig. 4
Fig. 4
Daily systemic injection of PTH elevated the ALP levels and reduced the SOST levels in the alveolar bone, which could be reversed by local stattic injection. Representative images of immunohistochemical staining of ALP (a) and SOST (b) in the OTM + PD, OTM + PD + PTH and OTM + PD + PTH + S groups, and relative quantitative analysis at days 7 and 14. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000 1 by one-way ANOVA with Tukey’s post hoc test
Fig. 5
Fig. 5
Daily systemic injection of PTH decreased osteoclast numbers and RANKL levels, and increased OPG levels, which could be reversed by local stattic injection. Representative images of TRAP staining (a), immunohistochemical staining of RANKL (b) and OPG (c) in the OTM + PD, OTM + PD + PTH and OTM + PD + PTH + S groups, and relative quantitative analysis at days 7 and 14. d Comparison of the RANKL/OPG ratio in each group. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000 1 by one-way ANOVA with Tukey’s post hoc test
Fig. 6
Fig. 6
IPTH promoted osteogenesis in vitro, which could be reduced by stattic. aAlp, Ibsp, Opn, Sp7, Pth1r, Cbfa1, Col1a1 and Bglap expression in each group. b Protein levels of RANKL and OPG. c RANKL and OPG mRNA levels and the RANKL/OPG ratio. d Protein levels of representative osteoblastic markers and p-STAT3 (Tyr705) and STAT3. e Alizarin red S staining and ALP staining. f Quantitative analysis of Alizarin red S staining. g Quantitative analysis of ALP. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.000 1 by one-way ANOVA with Tukey’s post hoc test
Fig. 7
Fig. 7
IPTH activated Wnt/β-catenin signalling, while inhibition of STAT3 activation suppressed this effect. a Colocalization of β-catenin and STAT3 by immunofluorescence. b β-catenin levels in nuclear fractions (active form) and whole cells. cAxin2 expression level. dCtnnb1 expression level. eSost expression level. f A diagram showing the hypothesis that PTH regulates STAT3 and Wnt/β-catenin signalling. *P < 0.05, **P < 0.01 by one-way ANOVA with Tukey’s post hoc test

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