title: Osteocytes produce interferon-β as a negative regulator of osteoclastogenesis.
abstract: Osteoclastogenesis is controlled by osteocytes; osteocytic osteoclastogenesis regulatory molecules are largely unknown. We searched for such factors using newly developed culture methods. Our culture system mimics the three-dimensional cellular structure of bone, consisting of collagen gel-embedded osteocytic MLO-Y4 cells, stromal ST2 cells on the gel as bone lining cells, and bone marrow cells. The gel-embedded MLO-Y4 cells inhibited the osteoclastogenesis induced by 1,25(OH)2D3 without modulating receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) production by ST2 cells, despite MLO-Y4 cells supported osteoclastogenesis in the absence of ST2 cells. In the bone marrow cell culture, the conditioned medium from MLO-Y4 cells decreased the capability of osteoclastic differentiation from the cells induced by macrophage colony-stimulating factor. This decreased capability was concomitant with an increase in protein kinase R mRNA expression and an inhibition of c-Fos translation. These changes were partially normalized by the simultaneous addition of an anti-interferon (IFN)-β neutralizing antibody to MLO-Y4 cell conditioned medium. To study primary osteocytes, we prepared non-osteocytic cell-free osteocyte-enriched bone fragments (OEBFs). When osteoclast precursors were induced by macrophage colony-stimulating factor in the presence of OEBFs, the generated cells exhibited a diminished capacity for osteoclastogenesis. OEBFs prepared from OPG-knock-out mice exhibited a similar effect, indicating OPG-independent inhibition. The addition of anti-IFN-β neutralizing antibody during the co-culture with OEBFs partially recovered the osteoclastogenic potential of the generated cells. The MLO-Y4 cells and OEBFs expressed IFN-β mRNA. Although osteocytic RANKL is known to be important for osteoclastogenesis, our data suggest that osteocytes also produce IFN-β as an inhibitor of osteoclastogenesis.
authors.affiliation: Division of Oral Anatomy and Meikai University School of Dentistry, Saitama 350-0283, Japan.
authors.forename: Chiyomi
authors.initials: C
authors.lastname: Hayashida
authors.affiliation: Division of Oral Anatomy and Meikai University School of Dentistry, Saitama 350-0283, Japan.
authors.forename: Junta
authors.initials: J
authors.lastname: Ito
authors.affiliation: Division of Orthodontics, Department of Human Development and Fostering, and Meikai University School of Dentistry, Saitama 350-0283, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Nakayachi
authors.affiliation: Division of Orthodontics, Department of Human Development and Fostering, and Meikai University School of Dentistry, Saitama 350-0283, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Okayasu
authors.affiliation: Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama 350-0283, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohyama
authors.affiliation: Division of Oral Anatomy and Meikai University School of Dentistry, Saitama 350-0283, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hakeda
authors.affiliation: Division of Oral Anatomy and Meikai University School of Dentistry, Saitama 350-0283, Japan. Electronic address: satotaku@dent.meikai.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016899:Interferon-beta; D016173:Macrophage Colony-Stimulating Factor; D002117:Calcitriol
keywords: Bone; Cytokines/Interferon; Osteoclast; Osteoclastogenesis; Osteocyte; Osteoporosis