Dental Science Research Institute and BK21, School of Dentistry, Chonnam National University, Gwangju, Korea.
BMB Rep. 2011 Nov;44(11):735-40. doi: 10.5483/BMBRep.2011.44.11.735.
Tunicamycin, an endoplasmic reticulum (ER) stress inducer, specifically inhibits N-glycosylation. The cyclic AMP (cAMP) response element-binding protein H (CREBH) was previously shown to be regulated by UPR-dependent proteolytic cleavage in the liver. On the other hand, the role of CREBH in other tissues is unknown. In the present study, tunicamycin increased the level of CREBH activation (cleavage) as well as mRNA expression in osteoblast cells. Adenoviral (Ad) overexpression of CREBH suppressed BMP2-induced expression of alkaline phosphatase (ALP) and osteocalcin (OC). Interestingly, the BMP2-induced OASIS (structurally similar to CREBH, a positive regulator of osteoblast differentiation) expression was also inhibited by CREBH overexpression. In addition, inhibition of CREBH expression using siRNA reversed the tunicamycin-suppressed ALP and OC expression. These results suggest that CREBH inhibited osteoblast differentiation via suppressing BMP2-induced ALP, OC and OASIS expression in mouse calvarial derived osteoblasts.
衣霉素是一种内质网（ER）应激诱导剂，特异性抑制 N-糖基化。先前的研究表明，环磷酸腺苷（cAMP）反应元件结合蛋白 H（CREBH）在肝脏中通过 UPR 依赖性蛋白水解切割进行调节。另一方面，CREBH 在其他组织中的作用尚不清楚。在本研究中，衣霉素增加了成骨细胞中 CREBH 激活（切割）的水平以及 mRNA 表达。腺病毒（Ad）过表达 CREBH 抑制了 BMP2 诱导的碱性磷酸酶（ALP）和骨钙素（OC）的表达。有趣的是，CREBH 过表达也抑制了 BMP2 诱导的 OASIS（与 CREBH 结构相似，是成骨细胞分化的正调节因子）的表达。此外，使用 siRNA 抑制 CREBH 的表达逆转了衣霉素抑制的 ALP 和 OC 的表达。这些结果表明，CREBH 通过抑制 BMP2 诱导的小鼠颅顶来源的成骨细胞中 ALP、OC 和 OASIS 的表达来抑制成骨细胞分化。
