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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00562

Sema3a as a novel therapeutic option for high glucose-suppressed osteogenic differentiation in diabetic osteopathy

 Lixia Zhang1,  Lili Zheng1, Chong Li1, Zhifang Wang1, Shan Li1 and  Lijun Xu1*
  • 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, China

Objective: Diabetic osteopathy is a common comorbidity of diabetes mellitus, with skeletal fragility, osteoporosis and bone pain. The aim of the present study was to highlight the role of sema3a on osteoblast differentiation of MC3T3-e1 in high-glucose condition and explore its therapeutic effect of diabetic osteopathy in vitro and vivo.

Methods: In this study, the effect of sema3a on osteoblast differentiation in high-glucose condition was evaluated by analyzing the expression of osteogenesis-related maker including ALP, OCN, OPG, β-catenin and Runx2, as well as ALP and Alizarin Red S staining in MC3T3 osteoblastic cells. In diabetic animal model, the expression of serum bone metabolic markers, such as ALP, P1NP, OCN and β-CTX, were analyzed and micro-CT was used to detect bone architecture including Tb.N, Tb.Th, Tb.Sp, Tb.Pf, BS/BV and BV/TV after the treatment of sema3a.
Results: High glucose significantly inhibited osteogenic differentiation by decreasing the expression of osteogenesis-related makers, sema3a and its receptor of Nrp-1 in a dose-dependent manner in MC3T3. In high-glucose condition, exogenous sema3a (RPL917Mu01) increased the expression of ALP, OCN, OPG, Runx2 and β-catenin in MC3T3, as well as the positive staining of ALP and Alizarin Red S. In addition, in diabetic animal model, exogenous sema3a could increase bone mass and bone mineral density, and downregulate the expression of ALP, P1NP, OCN and β-CTX.
Conclusion: High glucose suppresses osteogenic differentiation in MC3T3 and sema3a may take part in this process. The application of exogenous sema3a alleviates high glucose-induced inhibition of osteoblast differentiation in diabetic osteopathy.

Keywords: SEMA3A, Therapy -, Osteogenic differentiation, diabetes, Osteopathy

Received: 02 Apr 2019; Accepted: 02 Aug 2019.

Edited by:

Andrea Del Fattore, Bambino Gesù Children Hospital (IRCCS), Italy

Reviewed by:

Giulia Battafarano, Bambino Gesù Children Hospital (IRCCS), Italy
Helena Bacha Lopes, University of São Paulo, Brazil  

Copyright: © 2019 Zhang, Zheng, Li, Wang, Li and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Lijun Xu, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China, fahzzuendo@126.com