title: Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts.
abstract: Osteoclastogenesis inhibitory factor (OCIF) was previously reported to specifically inhibit osteoclast development by interrupting the action of osteoclast differentiation factor (ODF), which is expressed in stromal cells and plays an important role in osteoclastogenesis. Here we report the direct action of OCIF on isolated rabbit mature osteoclasts to inhibit their functional bone-resorbing activity. The cell population employed in this study consisted of mature osteoclasts with more than 95% of purity. The inhibition by OCIF was dose dependent and observed as early as 6 h after the OCIF addition. An OCIF-binding protein of 140 kDa was detected on the plasma membrane of osteoclasts. ODF with a Mr of 40 kDa was recently isolated as a ligand for OCIF and shows to be identical to TRANCE/RANKL. However, ODF was not detected in osteoclasts. OCIF did not have any impact on the mRNA levels of cathepsin K/OC2 and carbonic anhydrase II responsible for degradation of organic and inorganic bone matrices, respectively, or on osteoclast apoptosis. However, OCIF reduced or disrupted the formation of F-actin ring in isolated osteoclasts, the cytoskeletal structure of which is correlated with bone resorption. These findings demonstrate that OCIF directly inhibits osteoclast function through an ODF-independent mechanism besides blocking the generation of osteoclasts.
authors.affiliation: Department of Oral Anatomy, Meikai University School of Dentistry, Saitama, Sakado, 350-0283, Japan. y-hakeda@dent.meikai.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Hakeda
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: E
authors.initials: E
authors.lastname: Tsuda
authors.forename: K
authors.initials: K
authors.lastname: Higashio
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: M
authors.initials: M
authors.lastname: Kumegawa
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000818:Animals; D001862:Bone Resorption; D002256:Carbonic Anhydrases / Q000032:analysis; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects* / Q000648:ultrastructure; D053244:Osteoprotegerin; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D000199:Actins; D006023:Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D002403:Cathepsins; D056657:Cathepsin K; D002256:Carbonic Anhydrases