首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Synovial perlecan is required for osteophyte formation in knee osteoarthritis
Authors:Haruka Kaneko  Muneaki Ishijima  Ippei Futami  Naoki Tomikawa-Ichikawa  Keisuke Kosaki  Ryo Sadatsuki  Yoshihiko Yamada  Hisashi Kurosawa  Kazuo Kaneko  Eri Arikawa-Hirasawa
Institution:1. Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan;2. Department of Orthopedics, Juntendo University School of Medicine, Tokyo, Japan;3. Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan;4. Laboratory of Cell and Development Biology, NIDCR, NIH, Bethesda, MD, USA
Abstract:The osteophyte associated with osteoarthritis (OA) is a bony outgrowth formed at the margins of the affected joint through endochondral ossification-like processes. However, the mechanism of osteophyte formation and its pathogenesis are unclear. Perlecan (Hspg2), a heparan sulfate proteoglycan, is expressed in many extracellular tissues and plays critical roles in skeletal development and diseases. The aim of the present study is to identify the role of synovial perlecan in osteophyte formation using perinatal lethality rescued perlecan-knockout mice (Hspg2?/?-Tg) wherein perlecan expression is lacking in the synovial and other tissues, except for cartilage. We analyzed the development of osteophytes in joints of Hspg2?/?-Tg mice in two different animal models: the surgical OA model, in which the medial collateral ligament was transected and the medial meniscus was resected, and the TGF-β-induced osteophyte formation model. In the surgical OA model, the osteophyte size and maturation were significantly reduced in the OA joints of Hspg2?/?-Tg mice compared with control mice, while OA developed on the medial side of the knee joints with no differences in the cartilage degradation score or synovitis score between control and Hspg2?/?-Tg mice. The reduced osteophyte formation in Hspg2?/?-Tg mice was associated with reduced cell proliferation and chondrogenesis. In the TGF-β model, the osteophyte size and maturation were also significantly reduced in Hspg2?/?-Tg mice compared with control mice. Our findings suggest that synovial perlecan plays an important role in osteophyte development in OA, and they provide insights that may facilitate the development of OA therapy.
Keywords:
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号