Increased interleukin-6 production in mouse osteoblastic MC3T3-E1 cells expressing activating mutant of the stimulatory G protein

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
T MotomuraT Kishimoto

Abstract

The McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait spots, and multiple endocrine hyperfunction. An activating missense mutation of the alpha subunit of the Gs protein (Gs alpha) was found in several affected tissues, resulting in prolonged stimulation of adenylate cyclase. Our recent study has indicated that the cells derived from the fibrous bone dysplasia tissues in MAS patients produced increased levels of interleukin-6 (IL-6), which may be responsible for the increased bone resorption in this disease. In the present investigation, to analyze the molecular mechanism of the increased IL-6 production by activating mutant Gs alpha in bone cells, we established mouse osteoblastic MC3T3-E1 cells stably transfected with the activating mutant Gs alpha expression vector. These cells showed a significant increase of intracellular cAMP levels and produced a higher amount of IL-6 than the cells transfected with control vector or wild-type Gs alpha expression vector. Analysis of the IL-6 promoter revealed that any of the AP-1, nuclear factor (NF)-IL-6, and NF-kappa B binding elements are important for the activating mutant Gs alpha-induced gene expression. Electrophoretic mobility-shift as...Continue Reading

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Citations

Dec 8, 2009·Journal of Lipid Research·Wendy TsengYin Tintut
Mar 7, 2007·Calcified Tissue International·T-J ChoI H Choi
Jun 10, 2011·British Medical Bulletin·Angelo Del BuonoNicola Maffulli
Dec 18, 2001·Journal of Cellular Biochemistry·I ShurD Benayahu
Sep 8, 2004·Journal of Cellular Biochemistry·Irena ShurDafna Benayahu
Jan 19, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lee S Weinstein
Mar 30, 2011·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Aaron WallaceJohn D Lubahn
Nov 25, 2018·British Journal of Clinical Pharmacology·Marlous RotmanNatasha M Appelman-Dijkstra
Jul 18, 2008·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Hagen S BachmannChristian Wedemeyer
Aug 5, 2010·American Journal of Medical Genetics. Part a·János KissPéter Lakatos
Jul 18, 2002·Annals of the New York Academy of Sciences·Lee S WeinsteinJie Liu
Jun 8, 2001·Journal of Pediatric Endocrinology & Metabolism : JPEM·W ZumkellerM Nagel
Jan 12, 2001·Clinical Orthopaedics and Related Research·J M LaneJ Curtin

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