title: Chondromodulin-I derived from the inner meniscus prevents endothelial cell proliferation.
abstract: The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM-I. Immunohistochemical analyses revealed that ChM-I was mainly detected in the inner and superficial zones of the meniscus. On the other hand, endostatin distribution was similar between the inner and outer meniscus. In Western blot, ChM-I was detected only in the inner meniscus, whereas endostatin was equally observed in both inner and outer menisci. In addition, ChM-I concentration of the inner meniscus-derived conditioned medium was higher than that of the outer meniscus-derived medium. ChM-I removal from the inner meniscus-derived medium and functional blocking of ChM-I significantly increased endothelial cell proliferation. In this study, we demonstrated that the inner meniscus contained larger amounts of ChM-I, and that the inner meniscus-derived ChM-I inhibited endothelial cell proliferation. Our results suggest that ChM-I may be a key anti-angiogenic factor for maintaining the avascularity of the inner meniscus.
authors.affiliation: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Fujii
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furumatsu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kajiki
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Abe
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
mesh_terms: D000368:Aged; D019645:Arthroplasty, Replacement, Knee; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D043169:Endostatins / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D008592:Menisci, Tibial / Q000378:metabolism*
chemical_list: D043169:Endostatins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C068675:CNMD protein, human