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.