title: Retinoic acid receptor γ-dependent signaling cooperates with BMP2 to induce osteoblastic differentiation of C2C12 cells.
abstract: All-trans retinoic acid and bone morphogenetic protein 2 (BMP2) synergistically induced an alkaline phosphatase (ALP) activity, one of the osteoblastic differentiation markers, and promoted the extracellular matrix calcification in a myoblastic C2C12 cell culture system. The induced ALP mRNA was not suppressed in the presence of a protein synthesis inhibitor, suggesting that the de novo protein synthesis does not influence this induction. There are three isotypes for the retinoic acid receptor (RARα, RARβ, RARγ). Both the ALP activity and the extracellular matrix calcification were inhibited by the addition of the specific siRNA for RARγ, but not by that for RARα or RARβ. When the effects of the RAR subtype-specific agonists on the ALP activity in the presence of BMP2 were examined, the RARγ-specific agonist was the most effective. The ALP activity induced by any RAR subtype-specific agonist was inhibited by the addition of the specific siRNA for RARγ, but not by that for RARα or RARβ. These results suggest that a RARγ-dependent functional crosstalk is present between the retinoic acid and BMP2 signaling to induce osteogenic transdifferentiation in myoblastic C2C12 cells.
authors.affiliation: Department of Biochemistry, School of Dental Medicine, Tsurumi University , Yokohama , Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Karakida
authors.forename: Ryogo
authors.initials: R
authors.lastname: Yui
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukae
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Oida
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D032446:Myoblasts / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000502:physiology*; D012176:Retinoids / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000469:Alkaline Phosphatase; D055396:Bone Morphogenetic Protein 2; D003513:Cycloheximide; D011500:Protein Synthesis Inhibitors; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C525718:BMP2 protein, human; C445667:CD 666