Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Controls Endochondral Ossification through Hyaluronan Metabolism

Masayuki Shimoda, Hiroyuki Yoshida, Sakiko Mizuno, Toru Hirozane, Keisuke Horiuchi, Yuta Yoshino, Hideaki Hara, Yae Kanai, Shintaro Inoue, Muneaki Ishijima, Yasunori Okada

研究成果: Article

13 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)1162-1176
ページ数15
ジャーナルAmerican Journal of Pathology
187
発行部数5
DOI
出版物ステータスPublished - 2017 5 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

フィンガープリント Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Controls Endochondral Ossification through Hyaluronan Metabolism' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用