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Effects of combined menaquinone-4 and PTH1–34 treatment on osetogenesis and angiogenesis in calvarial defect in osteopenic rats

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Abstract

Purpose

The aim of this study was to evaluate the effect of combining human parathyroid hormone (1–34) (PTH1–34; PTH) and menaquinone-4 (MK-4) on calvarial bone defect repair in osteopenic rats.

Methods

Fourteen week olds were subject to craniotomy for the establishment of osteopenic animal models fed through a chronically low-protein diet. After that, critical calvarial defect model was established and all rats were randomly divided into four groups: sham, MK-4, PTH, and PTH + MK-4. The animals received MK-4 (30 mg/kg/day), PTH1–34 (60 μg/kg, three times a week), or PTH1–34 (60 μg/kg, three times a week) plus MK-4 (30 mg/kg/day) for 8 weeks, respectively. Serum γ-carboxylated osteocalcin (Gla-OC) levels, histological and immunofluorescent labeling were employed to evaluate the bone formation and mineralization in calvarial bone defect. In addition, Microfil perfusion, immunohistochemical, and micro-CT suggested enhanced angiogenesis and bone formation in calvarial bone healing.

Results

In this study, treatment with either PTH1–34 or MK-4 promoted bone formation and vascular formation in calvarial bone defects compared with the sham group. In addition, combined treatment of PTH1–34 plus MK-4 increased serum level of Gla-OC, improved vascular number and vascular density, and enhanced bone formation in calvarial bone defect in osteopenic conditions as compared with monotherapy.

Conclusions

In summary, this study indicated that PTH1–34 plus MK-4 combination therapy accelerated bone formation and angiogenesis in calvarial bone defects in presence of osteopenia.

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Acknowledgements

The study was supported by the Science Technology Department of Zhejiang Province (Grant No.:2016C37122), National Natural Science Foundation of China (Grant No.:81772348).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    She-Ji Weng, Zhong-Jie Xie, Zong-Yi Wu, De-Yi Yan, Jia-Hao Tang, Zi-Jian Shen, Hang Li, Bing-Li Bai, Viraj Boodhun & Lei Yang

  2. Department of Surgery, Westchester Medical Center / New York Medical College, Valhalla, NY, USA

    Xiang Da (Eric) Dong

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  1. She-Ji Weng
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Correspondence to Lei Yang.

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Animals were handled with the approval of the Animal Experimentation Ethics Committee of Second Affiliated Hospital of Wenzhou Medical University.

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Weng, SJ., Xie, ZJ., Wu, ZY. et al. Effects of combined menaquinone-4 and PTH1–34 treatment on osetogenesis and angiogenesis in calvarial defect in osteopenic rats. Endocrine 63, 376–384 (2019). https://doi.org/10.1007/s12020-018-1761-7

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