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  2. eIF2α-ATF4 Pathway Activated by a Change in the Calcium Environment Participates in BCP-Mediated Bone Regeneration

eIF2α-ATF4 Pathway Activated by a Change in the Calcium Environment Participates in BCP-Mediated Bone Regeneration

  • ACS Biomater Sci Eng. 2021 Jul 12;7(7):3256-3268. doi: 10.1021/acsbiomaterials.0c01802.
Zichao Xiang 1 2 Qionghui Wu 1 Yu Wang 1 3 Peng Wang 1 Yingyou He 1 Jihua Li 1
Affiliations

Affiliations

  • 1 West China Hospital of Stomatology, School of Stomatology, State Key Laboratory of Oral Diseases, and National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu 610000, China.
  • 2 The Affiliated Hospital of Stomatology, School of Stomatology, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310006, China.
  • 3 The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang 550001, China.
Abstract

Biphasic calcium phosphate (BCP) ceramic is a classic bone void filler and a common basis of new Materials for bone defect repair. However, the specific mechanism of BCP in osteogenesis has not been fully elucidated. Endoplasmic reticulum stress (ERs) and the subsequent PERK-eIF2α-ATF4 pathway can be activated by various factors, including trauma and intracellular calcium changes, and therefore worth exploring as a potential mechanism in BCP-mediated bone repair. Herein, a rat lateral femoral epicondyle defect model in vivo and a simulated BCP-mediated calcium environment in vitro were constructed for the analysis of BCP-related osteogenesis and the activation of ERs and the eIF2α-ATF4 pathway. An inhibitor of eIF2α dephosphorylation (salubrinal) was also used to explore the effect of the eIF2α-ATF4 pathway on BCP-mediated bone regeneration. The results showed that the ERs and eIF2α-ATF4 pathway activation were observed during 4 weeks of bone repair, with a rapid but brief increase immediately after artificial defect surgery and a re-increase after 4 weeks with the resorption of BCP Materials. Mild ERs and the activated eIF2α induced by the calcium changes mediated by BCP regulated the expression of osteogenic-related proteins and had an important role during the defect repair. In conclusion, the eIF2α-ATF4 pathway activated by a change in the calcium environment participates in BCP-mediated bone regeneration. eIF2α-ATF4 and ERs could provide new directions for further studies on new Materials in bone tissue engineering.

Keywords

bone regeneration; calcium phosphate ceramics; eIF2α−ATF4 pathway; endoplasmic reticulum stress.

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