RRC ID 37085
著者 Kaneshiro S, Otsuki D, Yoshida K, Yoshikawa H, Higuchi C.
タイトル MEK5 suppresses osteoblastic differentiation.
ジャーナル Biochem Biophys Res Commun
Abstract Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis.
巻・号 463(3)
ページ 241-7
公開日 2015-7-31
DOI 10.1016/j.bbrc.2015.05.035
PII S0006-291X(15)00949-3
PMID 25998381
MeSH Aniline Compounds / pharmacology Animals Cell Differentiation* / drug effects Cell Line Cell Proliferation / drug effects Indoles / pharmacology MAP Kinase Kinase 5 / antagonists & inhibitors MAP Kinase Kinase 5 / genetics MAP Kinase Kinase 5 / metabolism* Mice Mitogen-Activated Protein Kinase 7 / metabolism Osteoblasts / cytology* Osteoblasts / drug effects Osteoblasts / metabolism Phosphorylation / drug effects RNA Interference Up-Regulation
IF 2.985
引用数 6
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126) ST2(RCB0224) 293(RCB1637)