title: Regulation of osteoblast and osteoclast functions by FGF-6.
abstract: Fibroblast growth factor-6 (FGF-6) is known to be the key ligand for fibroblast growth factor receptor 4 (FGFR4) during muscle regeneration but its role in bone has yet to be verified. FGFR signaling is known to be important in the initiation and regulation of osteogenesis, so in this study the actions of FGF-6 on human osteoblasts and osteoclasts were investigated. Human primary osteoblasts (hOB) were used to study the effect of FGF-6 on proliferation (by ATP quantification), signal transduction (by ERK and AKT phosphorylation), differentiation (by alkaline phosphatase activity, APA), and mineralization (by calcein staining). To study FGF-6 activity on osteoclast differentiation, human bone marrow cells were used and tartrate-resistant acid phosphatase (TRAP) multinucleated cells together with actin filaments arrangements were quantified. Human primary mature osteoclasts were used to evaluate the effect of FGF-6 on osteoclast reabsorbing activity by reabsorbed pit measurements. FGF-6 >10(-9) M as FGF-2 10(-7) M induced hOB proliferation mediated by pERK together with a reduction in APA and reduced mineralization of the treated cells. Moreover FGF-6 increased the formation of TRAP-positive multinucleated cells in a dose-dependent manner (maximal effect at 10(-8) M). FGF-6-treated cells showed also a greater percentage of cells that formed typical osteoclast sealing zones. Mature osteoclasts cultured on dentine slice increased the area of reabsorption with a maximal effect of FGF-6 at 10(-12) M. FGF-6 may be considered a regulator of bone metabolism as shown by its activity on both osteoblasts and osteoclasts.
authors.affiliation: DISCAFF, Human Anatomy, University of Eastern Piedmont, Novara, Italy. bosetti@pharm.unipmn.it
authors.forename: Michela
authors.initials: M
authors.lastname: Bosetti
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Leigheb
authors.forename: Roger A
authors.initials: RA
authors.lastname: Brooks
authors.forename: Francesca
authors.initials: F
authors.lastname: Boccafoschi
authors.forename: Mario F
authors.initials: MF
authors.lastname: Cannas
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D051522:Fibroblast Growth Factor 6 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
chemical_list: C496452:FGF6 protein, human; D051522:Fibroblast Growth Factor 6; D007527:Isoenzymes; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase