title: Absence of herpes virus entry mediator (HVEM) increases bone mass by attenuating receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis.
abstract: Herpes virus entry mediator (HVEM), which is constitutively expressed at a high level on myeloid lineage cells, is also expressed on bone marrow-derived macrophages, suggesting that it may play a role in bone metabolism by affecting osteoclasts (OC) derived from bone marrow-derived macrophages. To address this question, we evaluated bone mass by micro-computed tomography and the number and activity of OC by tartrate-resistant acid phosphatase (TRAP) and pit formation on dentine slices, comparing HVEM-knockout mice with wild-type mice. The absence of HVEM led to a higher bone mass and to decreased levels of serum collagen type I fragments and serum TRACP5b in vivo. In vitro HVEM deficiency resulted in a reduced number and activity of OC and an impaired receptor activator of nuclear factor-κB ligand signaling through reduced activation of nuclear factor-κB and of nuclear factor of activated T-cells cytoplasmic 1. Exogenous soluble HVEM decreased expression of TRAP, whereas soluble LIGHT (a ligand of HVEM) increased it, indicating the occurrence of a positive signaling through HVEM during osteoclastogenesis. Our findings indicate that HVEM regulates bone remodeling via action on OC. The higher bone mass in the femurs of HVEM-knockout mice could be, at least in part, due to attenuated osteoclastogenesis and bone resorption resulting from decreased receptor activator of nuclear factor-κB ligand signaling in the OC.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680–749, Korea.
authors.forename: Woon-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Ok-Joo
authors.initials: OJ
authors.lastname: Sul
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Choi
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Lee
authors.forename: Choon-Soo
authors.initials: CS
authors.lastname: Jeong
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Suh
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015519:Bone Density / Q000502:physiology*; D001862:Bone Resorption / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse