Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the catabolic effects of mechanical strain in cementoblasts

Li, Yuyu; Hu, Zhangjian; Zhou, Chenchen; Xu, Yang; Huang, Li; Wang, Xin; Zou, Shujuan

doi:10.1186/s12860-017-0133-0

Cited by 22 publications

(27 citation statements)

References 40 publications

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“…Understanding the key regulators related to cementum formation during development and regeneration is pivotal for developing therapies to regenerate such tissue lost. Previous studies suggested that intermittent PTH promotes cementogenesis, but the underlying mechanisms remained inconclusive . In the present study, we investigated the anabolic effect of intermittent PTH on cellular cementum in developing teeth and addressed the interaction of PKA and ERK for cementogenesis.…”

Section: Discussionmentioning

confidence: 96%

“…Intermittent PTH administration increases bone mass by promoting osteoblast differentiation and proliferation and reducing osteoblast apoptosis, while continuous treatment decreases bone mass by activating osteoclast activity . In cementoblasts, continuous administration of PTH (1 to 34) modulates phosphate homeostasis by downregulating dentin matrix acidic phosphoprotein 1 (DMP1), whereas intermittent PTH facilitates cementum formation by promoting cementogenesis and elevating the expression of osteogenic differentiation biomarkers like osteocalcin (OCN), bone sialoprotein (BSP), collagen type I (COL1) . Moreover, intermittent PTH administration exerts anabolic effects on periodontal repair in rat tooth root resorption .…”

Section: Introductionmentioning

confidence: 99%

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Intermittent parathyroid hormone promotes cementogenesis in a PKA‐ and ERK1/2‐dependent manner

Zhang

et al. 2019

Journal of Periodontology

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Background: Intermittent parathyroid hormone (PTH) promotes cementogenesis and provides a promising biotherapeutic to rehabilitate resorbed roots. However, the underlying mechanisms remain inconclusive. Cyclic aenosine monophosphate (AMP)-dependent protein kinases A (PKA) and extracellular signal-regulated MAP kinases 1/2 (ERK1/2) are key regulators of bone remodeling. The present study aims to investigate whether PKA and ERK1/2 are involved in the process of intermittent PTH-promoted cementogenesis.Methods: Sprague-Dawley rats in experimental group (n = 30) received a daily subcutaneous injection of PTH and the control (n = 30) received placebo vehicle for 1, 2, 3, 4, and 5 weeks. Results were evaluated by hematoxylin and eosin and immunohistochemistry staining. In vitro, OCCM-30 cells were incubated with intermittent PTH. H89 and U0126 were used to determine the role of PKA and ERK1/2, respectively. The cementogenic results were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, alkaline phosphatase activity assay and Alizarin Red S staining. The interaction of PKA and p-ERK1/2 was determined by co-immunoprecipitation (Co-IP). Results:Intermittent PTH exerted anabolic effect on cellular cementum in developing teeth with elevated expression of osteocalcin, osteopontin, and PKA (catalytic subunit) in PTH injection group. The promoting effects of intermittent PTH on cementogenesis and osteogenic differentiation were abrogated by H89 and U0126 in vitro, respectively. Blocking of PKA pathway downregulated intermittent PTH-induced ERK1/2 phosphorylation. Conclusions:Intermittent PTH promotes cementogenesis in a PKA-and ERK1/2dependent manner. In this process, PKA and p-ERK1/2 interact with each other. These results support the future biotherapeutic applications of PTH in cementum resorption.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Intermittent parathyroid hormone promotes cementogenesis in a PKA‐ and ERK1/2‐dependent manner

Zhang

et al. 2019

Journal of Periodontology

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“…As the major regulator of bone remodeling and homeostasis, the mode of its administration determines its effects on bone (Ishizuya et al, 1997;Lombardi et al, 2011;Poole & Reeve, 2005). Recently, studies have focused on the physiological functions of PTH on periodontal tissues (Ge et al, 2020;Y. Li et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Intermittent parathyroid hormone promotes cementogenesis via ephrinB2‐EPHB4 forward signaling

Wang

et al. 2020

Journal Cellular Physiology

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Intermittent parathyroid hormone (PTH) promotes periodontal repair, but the underlying mechanisms remained unclear. Recent studies found that ephrinB2-EPHB4 forward signaling mediated the anabolic effect of PTH in bone homeostasis. Considering the similarities between cementum and bone, we aimed to examine the therapeutic effect of PTH on resorbed roots and explore the role of forward signaling in this process. In vivo experiments showed that intermittent PTH significantly accelerated the regeneration of root resorption and promoted expression of EPHB4 and ephrinB2. When the signaling was blocked, the resorption repair was also delayed. In vitro studies showed that intermittent PTH promoted the expression of EPHB4 and ephrinB2 in OCCM-30 cells. The effects of PTH on the mineralization capacity of OCCM-30 cells was mediated through the ephrinB2-EPHB4 forward signaling. These results support the premise that the anabolic effects of intermittent PTH on the regeneration of root resorption is via the ephrinB2-EPHB4 forward signaling pathway.

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“…[18][19][20][21] A number of in vitro studies have been conducted to investigate the osteogenic promoting effects of intermittent PTH treatment in various cells such as bone marrow MSCs, PDL-derived cells, cementoblasts, and odontoblasts. 20,[22][23][24] However, the effect of PTH on iPSCs in a three-dimensional (3D) has yet to be examined.…”

Section: Introductionmentioning

confidence: 99%

Effects of intermittent treatment with parathyroid hormone (PTH) on osteoblastic differentiation and mineralization of mouse induced pluripotent stem cells in a 3D culture model

Aoki

Nakamura

Onodera

et al. 2020

J of Periodontal Research

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Background/Objectives PTH plays an important role in bone remodeling, and different actions have been reported depending on its administration method. iPSCs are promising as a cell source for regeneration of periodontal tissue due to their ability of proliferation and pluripotency. However, the effects of PTH on iPSCs remain mostly unknown. The purpose of this study was to investigate in vitro effects of parathyroid hormone (PTH) on osteoblastic differentiation of induced pluripotent stem cells (iPSCs) in a 3D culture model. Materials and Methods Following embryoid body (EB) induction from mouse iPSCs (miPSCs), dissociated cells (miPS‐EB‐derived cells) were seeded onto atelocollagen sponge (ACS) in osteoblast differentiation medium (OBM). Cell‐ACS constructs were divided into three groups: continuous treatment with human recombinant PTH (1‐34) (PTH‐C), intermittent PTH treatment (PTH‐I) or OBM control. To confirm the expression of PTH receptor‐1(PTH1R), the expression of Pth1r and cAMP production over time were assessed. Real‐time PCR was used to assess the expression of genes encoding osterix (Sp7), runt‐related transcription factor 2 (Runx2), collagen type 1 (Col1a1), and osteocalcin (Bglap) at different time points. Mineralization was assessed by von Kossa staining. Histochemical staining was used to analyze alkaline phosphatase (ALP) activity, and immunolocalization of SP7 and BGLAP was analyzed by confocal laser scanning microscopy (CLSM). Results On days 7 and 14, expression of the Pth1r in miPS‐EB‐derived cells was increased in all groups. Production of cAMP, the second messenger of the PTH1R, tended to increase in the PTH‐I group compared with PTH‐C group on day 14. Expression of Col1a1 in the PTH‐I group on day 14 was significantly higher than other groups. There was a time‐dependent increase in the expression of Sp7 in all groups. On day 14, the expression level of Sp7 in the PTH‐I group was significantly higher than other groups. In von Kossa staining, the PTH‐I group showed higher level of staining compared with other groups on day 14, whereas the level was slightly attenuated in the PTH‐C group. In histochemical staining, ALP‐positive cells were significantly increased in the PTH‐I group compared with other groups on day 14. In CLSM analysis, the numbers of SP7‐ and BGLAP‐positive cells showed a gradual increase over time, and on day 14, a significantly greater SP7 expression was observed in the PTH‐I group than other groups. Conclusion These results suggested that the intermittent PTH treatment promotes osteoblastic differentiation and mineralization of miPSCs in the ACS scaffold.

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Intermittent parathyroid hormone (PTH) promotes cementogenesis and alleviates the catabolic effects of mechanical strain in cementoblasts

Cited by 22 publications

References 40 publications

Intermittent parathyroid hormone promotes cementogenesis in a PKA‐ and ERK1/2‐dependent manner

Intermittent parathyroid hormone promotes cementogenesis in a PKA‐ and ERK1/2‐dependent manner

Intermittent parathyroid hormone promotes cementogenesis via ephrinB2‐EPHB4 forward signaling

Effects of intermittent treatment with parathyroid hormone (PTH) on osteoblastic differentiation and mineralization of mouse induced pluripotent stem cells in a 3D culture model

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