Research Paper Volume 12, Issue 1 pp 387—396

Osteocalcin improves outcome after acute ischemic stroke

Jiayan Wu 1, , Yunxiao Dou 1, , Wangmi Liu 2, , Yanxin Zhao 1, , Xueyuan Liu 1, ,

  • 1 Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai 200032, China
  • 2 The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China

received: November 6, 2019 ; accepted: December 18, 2019 ; published: January 5, 2020 ;

https://doi.org/10.18632/aging.102629
How to Cite

Copyright © 2020 Wu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Osteocalcin is related to energy metabolism, memory and the acute stress response, suggesting a relationship between bone and the brain. The need to explore the effect of osteocalcin on acute ischemic stroke is therefore urgent.

Results: Patients with better outcomes had higher serum osteocalcin levels than those whose NIHSS scores did not improve. Multivariable logistic regression analysis showed acceptable performance (area under the curve = 0.766). The effect of osteocalcin on the promotion of neuron survival was confirmed by Cell Counting Kit-8 experiments. In addition, osteocalcin could decrease proline hydroxylase 1 and inhibit the degradation of gasdermin D.

Conclusions: We propose that osteocalcin can improve outcome after acute ischemic stroke in the acute period. By downregulating proline hydroxylase 1, osteocalcin leads glucose metabolism to the pentose phosphate pathway and therefore promotes neuronal survival through inhibiting pyroptosis.

Methods: Demographic data and laboratory results were obtained from patients with ischemic stroke in the acute period for analysis. A receiver operating characteristic curve was used to assess the discrimination of the prediction model. The potential effect of osteocalcin on cerebral ischemia and osteocalcin mechanism were explored in cultured primary rat cerebral cortical neurons treated with oxygen-glucose deprivation and reoxygenation.

Abbreviations

BDNF: brain-derived neurotrophic factor; GBDT: gradient boosting decision tree; NIHSS: National Institutes of Health Stroke Scale; OGD/R: oxygen-glucose deprivation and reoxygenation; PHD1: proline hydroxylase 1; ROC: receiver operating characteristic; RT-PCR: Real-time PCR; TCVs: transcortical vessels.