title: Tunicamycin negatively regulates BMP2-induced osteoblast differentiation through CREBH expression in MC3T3E1 cells.
abstract: 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.
authors: Dental Science Research Institute and BK21, School of Dentistry, Chonnam National University, Gwangju, Korea.
authors: Won Gu
authors: WG
authors: Jang
authors: Eun Jung
authors: EJ
authors: Kim
authors: Jeong-Tae
authors: JT
authors: Koh
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; C119923:Creb3l1 protein, mouse; C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D015675:Osteocalcin; D014415:Tunicamycin; D000469:Alkaline Phosphatase