title: Osteoclast development in immobilized bone is suppressed by parathyroidectomy in mice.
abstract: We tested the hypothesis that signaling of parathyroid hormone (PTH) facilitates osteoclastogenesis in bone marrow cells after immobilization, thereby reducing trabecular bone volume. We performed histomorphometric analyses in immobilized limbs after right sciatic neurectomy (IM) and in the contralateral limbs after sham surgery (M). Mice underwent thyroparathyroidectomy (TPTX) and then 0.2 microg/body of thyroxine was given three times a week, or the mice were subjected to sham surgery (sham). Six-week-old male ddY mice were assigned to four groups, as follows, after acclimatization for 1 week: M + sham, IM + sham; M + TPTX, and IM + TPTX. Bilateral tibial samples were used for analysis. Trabecular bone volume (BV/TV) in the secondary spongiosa of the proximal tibias in IM + sham was significantly reduced compared to that in M + sham. Osteoclast surface (Oc.S/BS) and number (Oc.N/BS) in IM + sham transiently increased at 3 and 4 weeks after IM. In contrast, TPTX partially prevented the IM-related reduction of BV/TV and completely suppressed the transient increases of Oc.S/BS and Oc.N/BS. In the bone marrow cells, the mRNA expression of RANKL was elevated in IM + sham, but not in IM + TPTX, compared to that in M + sham. The percentage of Mac-1-positive bone marrow cells, osteoclast precursors, was not altered after IM. There were no significant differences in the concentrations of interleukin (IL)-1alpha in the tibial bone marrow cell culture medium between M + sham and IM + sham. Our data demonstrated that significant increases in osteoclast surface and number after IM were suppressed in TPTX mice, closely associated with a reduction in the high expression of RANKL mRNA in the tibial bone marrow cells. We speculate that enhanced osteoclastogenesis due to limb immobilization may be related to the elevation of RANKL expression by the facilitation of parathyroid hormone signaling in bone marrow cells.
authors.affiliation: Department of Orthopaedic Surgery, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. a-sakai@med.uoeh-u.ac.jp
authors.forename: Akinori
authors.initials: A
authors.lastname: Sakai
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Mori
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sakuma-Zenke
authors.forename: Tomonori
authors.initials: T
authors.lastname: Takeda
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nakai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Katae
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hirasawa
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology / Q000166:cytology*; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D006023:Glycoproteins / Q000235:genetics; D019417:Hindlimb Suspension; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009929:Organ Size; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D053244:Osteoprotegerin; D016105:Parathyroidectomy; D010758:Phosphorus / Q000097:blood; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; 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; D010758:Phosphorus; D002118:Calcium