title: Role of osteoglycin in the linkage between muscle and bone.
abstract: The interaction between muscle tissues and bone metabolism is incompletely understood. We hypothesized that there might be some humoral factors that are produced in muscle tissues and exhibit bone anabolic activity. We, therefore, performed comparative DNA microarray analysis between mouse myoblastic C2C12 cells transfected with either stable empty vector or ALK2 (R206H), the mutation that constitutively activates the bone morphogenetic protein (BMP) receptor, to search for muscle-derived bone anabolic factors. Twenty-five genes whose expression was decreased to <1/4, were identified; these included osteoglycin (OGN). Stable overexpression of OGN significantly decreased the levels of Runx2 and Osterix mRNA compared with those in cells transfected with vector alone in MC3T3-E1 cells. On the other hand, it significantly enhanced the levels of alkaline phosphatase (ALP), type I collagen (Col1), and osteocalcin (OCN) mRNA as well as β-catenin and mineralization. A reduction in endogenous OGN level showed the opposite effects to those of OGN overexpression in MC3T3-E1 and mouse calvarial osteoblastic cells. Transient OGN overexpression significantly suppressed the levels of Runx2, Osterix, ALP, Col1, and OCN mRNA induced by BMP-2 in C2C12 cells. The conditioned medium from OGN-overexpressed and OGN-suppressed myoblastic cells enhanced and decreased, respectively, the levels of ALP, Col1, and β-catenin in MC3T3-E1 cells. Moreover, OGN increased Smad3/4-responsive transcriptional activity as well as Col1 mRNA levels independently of endogenous TGF-β in these cells. In conclusion, this study suggests that OGN may be a crucial humoral bone anabolic factor that is produced by muscle tissues.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Erika
authors.initials: E
authors.lastname: Matsumoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Higashimaki
authors.forename: Takenobu
authors.initials: T
authors.lastname: Katagiri
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D020125:Mutation, Missense; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D061251:Primary Cell Culture; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D036341:Intercellular Signaling Peptides and Proteins; C512906:Ogn protein, mouse; D016212:Transforming Growth Factor beta; D030201:Activin Receptors, Type I