title: FAM5C is a soluble osteoblast differentiation factor linking muscle to bone.
abstract: Muscle mass is related to higher bone mass and a reduction in fracture risk. However, the interactions between muscle tissues and bone metabolism are incompletely understood and there might be some humoral factors that are produced in muscle tissues and exhibit bone anabolic activity. We therefore investigated the role of FAM5C in osteoblast differentiation and the interactions between muscle and bone. A reduction of endogenous FAM5C by siRNA reduced the levels of osterix, alkaline phosphatase (ALP) and osteocalcin (OCN) mRNA as well as the levels of type 1 collagen and β-catenin in mouse osteoblastic MC3T3-E1 cells and mouse calvarial osteoblasts, although FAM5C overexpression significantly antagonized the levels of osterix, ALP and OCN mRNA induced by bone morphogenetic protein-2 in C2C12 cells. The conditioned medium from FAM5C-overexpressed and -suppressed C2C12 cells increased and decreased the levels of osterix, ALP and OCN mRNA in MC3T3-E1 cells, respectively. In conclusion, the present study is the first to show that FAM5C enhances osteoblast differentiation in differentiated osteoblasts, and that the effects of the conditioned medium from FAM5C-modulated myoblastic cells were positively correlated with the effects of FAM5C on osteoblast phenotype in osteoblasts. FAM5C might be an important humoral bone anabolic factor produced from muscle cells.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. ken1nai@med.shimane-u.ac.jp
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: 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: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D017077:Culture Media, Conditioned; C571157:FAM5C protein, mouse; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D051176:beta Catenin; D015675:Osteocalcin; D000469:Alkaline Phosphatase