title: Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-kappaB ligand.
abstract: Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption. Serum concentrations of RANKL are extremely high in OPG-deficient (OPG(-/-)) mice, suggesting that circulating RANKL is involved in osteoclastogenesis. RANKL(-/-) mice exhibit osteopetrosis, with the absence of osteoclasts. We examined the requirements for osteoclastogenesis using OPG(-/-) mice, RANKL(-/-) mice, and a system involving bone morphogenetic protein 2 (BMP-2)-induced ectopic bone formation. When collagen disks containing BMP-2 (BMP-2-disks) or vehicle were implanted into OPG(-/-) mice, osteoclast-like cells (OCLs) and alkaline phosphatase-positive OCLs appeared in BMP-2-disks but not the control disks. F4/80-positive osteoclast precursors were similarly distributed in both BMP-2- and control disks. Cells expressing RANKL were detected in the BMP-2-disks, and the addition of OPG to the disk inhibited OCL formation. Muscle cells in culture differentiated into alkaline phosphatase-positive cells in the presence of BMP-2 and accordingly expressed RANKL mRNA in response to PTH. This suggests that RANKL expressed by osteoblasts is a requirement for osteoclastogenesis. We then examined how osteoblasts are involved in osteoclastogenesis other than RANKL expression, using RANKL(-/-) mice. BMP-2- and control disks were implanted into RANKL(-/-) mice, which were injected with RANKL for 7 d. Many OCLs were observed in the BMP-2-disks and bone tissues but not the control disks. These results suggest that osteoblasts also play important roles in osteoclastogenesis through offering the critical microenvironment for the action of RANKL.
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi-Gakuin University, 464-8650 Aichi, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamichi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horiuchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hosoya
authors.forename: Midori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Ozawa
authors.forename: Kunio
authors.initials: K
authors.lastname: Takaoka
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D003094:Collagen