BMP-2 Enhances Lgr4 Gene Expression in Osteoblastic Cells.
Osteoporosis is one of the most prevalent diseases and the number of patients suffering from this disease is soaring due to the increase in the aged population in the world. The severity of bone loss in osteoporosis is based on the levels of impairment in the balance between bone formation and bone resorption, two arms of the bone metabolism, and bone remodeling. However, determination of bone formation levels is under many layers of control that are as yet fully defined. Bone morphogenetic protein (BMP) plays a key role in regulation of bone formation while its downstream targets are still incompletely understood. Lgr4 gene encodes an orphan receptor and has been identified as a genetic determinant for bone mass in osteoporotic patients. Here, we examine the effects of BMP on the expression of Lgr4 in osteoblastic cells. Lgr4 gene is expressed in an osteoblastic cell line, MC3T3E1 in a time dependent manner during the culture. BMP treatment enhances Lgr4 mRNA expression at least in part via transcriptional event. When Lgr4 mRNA is knocked down, the levels of BMP-induced increase in alkaline phosphatase (Alp) activity and Alp mRNA are suppressed. BMP enhancement of Lgr4 gene expression is suppressed by FGF and reversed by dexamethasone. BMP also enhances Lgr4 expression in primary cultures of calvarial osteoblasts. These data indicate that Lgr4 gene is regulated by BMP and is required for BMP effects on osteoblastic differentiation. J. Cell. Physiol. 231: 887-895, 2016. © 2015 Wiley Periodicals, Inc.
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.|Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
Chantida
C
Pawaputanon Na Mahasarakham
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Yoichi
Y
Ezura
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Makiri
M
Kawasaki
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Arayal
A
Smriti
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Shuichi
S
Moriya
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Takayuki
T
Yamada
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Yayoi
Y
Izu
Department of Pharmacology, Tsurumi University, School of Dental Medicine, Japan.
Akira
A
Nifuji
Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Japan.
Katsuhiko
K
Nishimori
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
Yuichi
Y
Izumi
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Masaki
M
Noda
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C496200:LGR4 protein, mouse; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000469:Alkaline Phosphatase