title: Actions of fibroblast growth factor-8 in bone cells in vitro.
abstract: The fibroblast growth factors (FGFs) are a group of at least 25 structurally related peptides that are involved in many biological processes. Some FGFs are active in bone, including FGF-1, FGF-2, and FGF-18, and recent evidence indicates that FGF-8 is osteogenic, particularly in mesenchymal stem cells. In the current study, we found that FGF-8 was expressed in rat primary osteoblasts and in osteoblastic UMR-106 and MC3T3-E1 cells. Both FGF-8a and FGF-8b potently stimulated the proliferation of osteoblastic cells, whereas they inhibited the formation of mineralized bone nodules in long-term cultures of osteoblasts and reduced the levels of osteoblast differentiation markers, osteocalcin, and bone sialoprotein. FGF-8a induced the phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) in osteoblastic cells; however, its mitogenic actions were not blocked by either the MAPK kinase (MEK) inhibitor U-0126 or the PI 3-kinase (PI3K) inhibitor LY-294002. Interestingly, FGF-8a, unlike FGF-8b and other members of the family, inhibited osteoclastogenesis in mouse bone marrow cultures, and this was via a receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG)-independent manner. However, FGF-8a did not affect osteoclastogenesis in RAW 264.7 cells (a macrophage cell line devoid of stromal cells) exogenously stimulated by RANKL, nor did it affect mature osteoclast function as assessed in rat calvarial organ cultures and isolated mature osteoclasts. In summary, we have demonstrated that FGF-8 is active in bone cells, stimulating osteoblast proliferation in a MAPK-independent pathway and inhibiting osteoclastogenesis via a RANKL/OPG-independent mechanism. These data suggest that FGF-8 may have a physiological role in bone acting in an autocrine/paracrine manner.
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Lin
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: Maureen
authors.initials: M
authors.lastname: Watson
authors.forename: Victoria
authors.initials: V
authors.lastname: Empson
authors.forename: Pak C
authors.initials: PC
authors.lastname: Tong
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
authors.forename: Dorit
authors.initials: D
authors.lastname: Naot
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018031:Connexin 43; D051524:Fibroblast Growth Factor 8; D019950:Mitogen-Activated Protein Kinase 1