title: Osteogenic protein-1 (OP-1, BMP-7) induces osteoblastic cell differentiation of the pluripotent mesenchymal cell line C2C12.
abstract: The effects of Osteogenic Protein-1 (OP-1, BMP-7) on the differentiation of the pluripotent mesenchymal cell line, C2C12, were examined. OP-1 at 50 ng/ml partially inhibited myotube formation in C2C12 cells, while OP-1 at 200 ng/ml completely inhibited myotube formation and induced the formation of cells displaying osteoblastic morphology. High concentrations of OP-1 elevated the alkaline phosphatase (AP) activity dramatically, both as a function of time and OP-1 concentration. Osteocalcin (OC) mRNA expression was detected as early as 8 days in OP-1-treated cultures and subsequently increased considerably. Expression of bone sialoprotein (BSP) mRNA was low in control cultures and stimulated by OP-1. Collagen type I mRNA expression was enhanced by OP-1 during the early days in culture, but gradually decreased thereafter. MyoD mRNA expression, high in control cultures, was suppressed by OP-1 in a dose- and time-dependent manner. OP-1 enhanced ActR-I mRNA expression and significantly elevated the mRNA expressions of BMP-1, BMP-4, BMP-5, GDF-6, and GDF-8. The present results indicate that OP-1 is a potent inducer of C2C12 differentiation into osteoblastic cells.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. carolyeh@biochem.uthscsa.edu
authors.forename: Lee-Chuan C
authors.initials: LC
authors.lastname: Yeh
authors.forename: Alicia D
authors.initials: AD
authors.lastname: Tsai
authors.forename: John C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008858:Microscopy, Phase-Contrast; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D016212:Transforming Growth Factor beta
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C546871:IBSP protein, human; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D052004:Bone Morphogenetic Protein Receptors; D000469:Alkaline Phosphatase