title: Synovial perlecan is required for osteophyte formation in knee osteoarthritis.
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.
authors: Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan. harukago@juntendo.ac.jp
authors: Haruka
authors: H
authors: Kaneko
authors: Muneaki
authors: M
authors: Ishijima
authors: Ippei
authors: I
authors: Futami
authors: Naoki
authors: N
authors: Tomikawa-Ichikawa
authors: Keisuke
authors: K
authors: Kosaki
authors: Ryo
authors: R
authors: Sadatsuki
authors: Yoshihiko
authors: Y
authors: Yamada
authors: Hisashi
authors: H
authors: Kurosawa
authors: Kazuo
authors: K
authors: Kaneko
authors: Eri
authors: E
authors: Arikawa-Hirasawa
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000502:physiology; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D054850:Osteophyte / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051899:Smad2 Protein / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D024022:Fibrillar Collagens; D019812:Heparan Sulfate Proteoglycans; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; C071927:perlecan