title: Regulation of Osteoblast Migration Involving Receptor Activator of Nuclear Factor-kappa B (RANK) Signaling.
abstract: Bone remodeling requires osteoclast activation, resorption, and reversal, prior to osteoblast migration into the bone pit. The Receptor Activator of NF-κB (RANK) signaling pathway plays an important role in bone remodeling. Two components of the RANK signaling pathway, RANK Ligand (RANKL) and the decoy receptor Osteoprotegerin (OPG), are expressed predominantly on the surface of osteoblasts, while RANK is principally expressed on the surface of osteoclasts. However, RANK has also been reported to be expressed on the surface of osteoblasts and osteosarcoma tumor cells. Treatment with soluble RANKL (sRANKL) of both normal osteoblasts and osteosarcoma tumor cells activated phosphorylation of ERK, p38(MAPK) , Akt, and p65(NF-κB). However, modified Boyden chamber assays and wound repair assays showed differential response to sRANKL-induced chemotactic migration in normal osteoblasts and osteosarcoma tumor cells. In contrast to previously published results, both normal osteoblasts and osteosarcoma tumor cells responded to sRANKL-induced chemotactic migration but the normal osteoblasts did so only in the presence of an ERK pathway inhibitor. For both normal and tumor cells, the chemotactic response could be blocked by inhibiting the PI3K/Akt or p65(NF-κB) pathway. Response to sRANKL in normal and tumor cells suggests a role for RANK/ERK-mediated signaling in normal osteoblasts chemotactic migration during bone remodeling that is altered or lost during osteosarcoma tumorigenesis.
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Diana
authors.initials: D
authors.lastname: Golden
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Saria
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hansen
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D016723:Bone Remodeling; D045744:Cell Line, Tumor; D002633:Chemotaxis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C498143:RELA protein, human; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; D051996:Transcription Factor RelA; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases