title: BMP-2 and titanium particles synergistically activate osteoclast formation.
abstract: A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.
authors.affiliation: Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
authors.forename: S X
authors.initials: SX
authors.lastname: Sun
authors.affiliation: Ningxia Medical University, Ningxia Hui Autonomous Region, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Guo
authors.affiliation: Institute of Pathology, Xi'an Jiaotong University, Xi'an Shaanxi, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ningxia Medical University, Ningxia Hui Autonomous Region, China.
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
authors.forename: K N
authors.initials: KN
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
authors.forename: Q H
authors.initials: QH
authors.lastname: Jin
mesh_terms: D000135:Acid Phosphatase / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D007527:Isoenzymes / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D051785:Smad Proteins / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D014025:Titanium / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D007527:Isoenzymes; D053245:RANK Ligand; D051785:Smad Proteins; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase