title: Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Controls Endochondral Ossification through Hyaluronan Metabolism.
abstract: Hyaluronan (HA) plays an important role in the development and maintenance of tissues, and its degradation is implicated in many pathologic conditions. We recently reported that HA-binding protein involved in HA depolymerization (CEMIP; alias HYBID/KIAA1199) is a key molecule in HA depolymerization, but its developmental and pathologic functions remain elusive. We generated Hybid-deficient mice using the Cre/locus of crossover in P1 (loxP) system and analyzed their phenotypes. Hybid-deficient mice were viable and fertile, but their adult long bones were shorter than those of wild-type animals. Hybid-deficient mice showed lengthening of hypertrophic zone in the growth plate until 4 weeks after birth. There were fewer capillaries and osteoclasts at the chondroosseous junction in the Hybid-deficient mice compared with the wild-type mice. In situ hybridization demonstrated that Hybid was expressed by hypertrophic chondrocytes at the chondroosseous junction. Cultured primary chondrocytes expressed higher levels of Hybid than did osteoblasts or osteoclasts, and the Hybid expression in the chondrocytes was up-regulated after maturation to hypertrophic chondrocytes. High-molecular-weight HA was accumulated in the lengthened hypertrophic zone in Hybid-deficient mice. In addition, high-molecular-weight HA significantly reduced cell growth and tube formation in vascular endothelial growth factor-stimulated or -nonstimulated endothelial cells. HA metabolism by HYBID is involved in endochondral ossification during postnatal development by modulation of angiogenesis and osteoclast recruitment at the chondroosseous junction.
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan. Electronic address: shimoda@a2.keio.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Biological Science Research, Kao Corporation, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hirozane
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshino
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Orthopaedic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Muneaki
authors.initials: M
authors.lastname: Ishijima
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan; Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: ya-okada@juntendo.ac.jp.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D006132:Growth Plate / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism*; D051379:Mice; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*
chemical_list: D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid