eIF2α-ATF4 Pathway Activated by a Change in the Calcium Environment Participates in BCP-Mediated Bone Regeneration.
Zichao XiangQionghui WuYu WangPeng WangYingyou HeJi-Hua LiPublished in: ACS biomaterials science & engineering (2021)
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.
Keyphrases
- bone regeneration
- endoplasmic reticulum stress
- transcription factor
- induced apoptosis
- bone mineral density
- mesenchymal stem cells
- minimally invasive
- tissue engineering
- oxidative stress
- risk assessment
- soft tissue
- coronary artery disease
- postmenopausal women
- signaling pathway
- percutaneous coronary intervention
- quantum dots
- atrial fibrillation
- preterm birth
- sensitive detection
- gestational age