Hyaluronan (HA)-
binding protein involved in HA depolymerization (HYBID) is involved in cartilage destruction via HA depolymerization in human
knee osteoarthritis. However, the role of HYBID in the progression of
osteoarthritis remain elusive. This study sought to examine whether genetic depletion of Hybid could suppress surgically induced
osteoarthritis of mouse knee joints. In
osteoarthritis induced by medial collateral ligament transection with meniscus removal, articular cartilage destruction and
osteophyte formation at the medial femoral-tibial joint were significantly inhibited in Hybid-deficient (Hybid-/-) mice compared with wild-type mice. Hybid was highly produced by synovial cells and articular chondrocytes in the
osteoarthritis joints of wild-type mice. IL-1β,
IL-6, and
tumor necrosis factor-α were up-regulated in the
osteoarthritis joint tissues of both wild-type and Hybid-/- mice. Vascular density at the synovial and periosteal junction was significantly reduced in Hybid-/- mice compared with wild-type mice. High-molecular-weight HA accumulated in
osteoarthritis joint tissues of Hybid-/- mice.
Injections of high-molecular-weight HA to knee joints attenuated the cartilage destruction and
osteophyte formation in wild-type mouse
osteoarthritis group. Inhibition of cartilage destruction and
osteophyte formation in Hybid-/- mice was also observed in destabilization of the medial meniscus model. These data are the first to demonstrate that cartilage destruction and
osteophyte formation are suppressed in Hybid-/- mice and suggest that Hybid-mediated HA depolymerization is implicated for the progression of mechanically-induced
knee osteoarthritis.