Absence of Herpes Virus Entry Mediator (HVEM) Increases Bone Mass by Attenuating Receptor Activator of Nuclear Factor-κB ligand (RANKL)-Induced Osteoclastogenesis

• Published in: Endocrinology (Philadelphia) 2012-10, Vol.153 (10), p.4808-4817
• Main Authors: Kim, Woon-Ki, Sul, Ok-Joo, Choi, Eun-Kyung, Lee, Mi-Hyun, Jeong, Choon-Soo, Kim, Hyun-Ju, Kim, Shin-Yoon, Suh, Jae-Hee, Yu, Rina, Choi, Hye-Seon
• Format: Article
• Language: English
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Animals; Apoptosis - physiology; Biological and medical sciences; Bone Density - physiology; Bone marrow; Bone mass; Bone remodeling; Bone resorption; Bone Resorption - metabolism; Bone turnover; Cell activation; Collagen (type I); Collagen Type I - blood; Computed tomography; Fundamental and applied biological sciences. Psychology; Herpes viruses; Herpesvirus; Human viral diseases; Infectious diseases; Ligands; Macrophages; Medical sciences; Mice; Mice, Knockout; Osteoclastogenesis; Osteoclasts; Osteoclasts - cytology; Osteoclasts - metabolism; Peptide Fragments - blood; RANK Ligand - genetics; RANK Ligand - metabolism; Reactive Oxygen Species - metabolism; Receptors; Receptors, Tumor Necrosis Factor, Member 14 - genetics; Receptors, Tumor Necrosis Factor, Member 14 - metabolism; Vertebrates: endocrinology; Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2012-1079

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.