Department of Joint Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266003, China.
Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
J Transl Med. 2023 Jul 18;21(1):480. doi: 10.1186/s12967-023-04328-8.
Bone regeneration therapy is clinically important, and targeted regulation of endoplasmic reticulum (ER) stress is important in regenerative medicine. The processing of proteins in the ER controls cell fate. The accumulation of misfolded and unfolded proteins occurs in pathological states, triggering ER stress. ER stress restores homeostasis through three main mechanisms, including protein kinase-R-like ER kinase (PERK), inositol-requiring enzyme 1ɑ (IRE1ɑ) and activating transcription factor 6 (ATF6), collectively known as the unfolded protein response (UPR). However, the UPR has both adaptive and apoptotic effects. Modulation of ER stress has therapeutic potential for numerous diseases. Repair of bone defects involves both angiogenesis and bone regeneration. Here, we review the effects of ER stress on osteogenesis and angiogenesis, with emphasis on ER stress under high glucose (HG) and inflammatory conditions, and the use of ER stress inducers or inhibitors to regulate osteogenesis and angiogenesis. In addition, we highlight the ability for exosomes to regulate ER stress. Recent advances in the regulation of ER stress mediated osteogenesis and angiogenesis suggest novel therapeutic options for bone defects.
骨再生治疗具有重要的临床意义，而内质网（ER）应激的靶向调节在再生医学中很重要。ER 中蛋白质的加工控制着细胞命运。在病理状态下，错误折叠和未折叠的蛋白质积累，引发 ER 应激。ER 应激通过三种主要机制恢复内稳态，包括蛋白激酶 R 样内质网激酶（PERK）、肌醇需求酶 1α（IRE1α）和激活转录因子 6（ATF6），统称为未折叠蛋白反应（UPR）。然而，UPR 既有适应性又有凋亡性。ER 应激的调节对许多疾病具有治疗潜力。骨缺损的修复涉及血管生成和骨再生。在这里，我们综述了 ER 应激对成骨和血管生成的影响，重点介绍了高糖（HG）和炎症条件下的 ER 应激，以及 ER 应激诱导剂或抑制剂在调节成骨和血管生成中的作用。此外，我们强调了外泌体调节 ER 应激的能力。ER 应激介导的成骨和血管生成的最新研究进展为骨缺损的治疗提供了新的选择。
