Deletion of Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization (HYBID) Results in Attenuation of Osteoarthritis in Mice

Masayuki Shimoda,Yoko Endo,Kazuo Kaneko,Tomomi Nakamura,Susana De Vega,Haruka Kaneko,Muneaki Ishijima,Masahiro Momoeda,Yasunori Okada,Chiho Yoshinaga,Hiroyuki Yoshida

doi:10.1016/j.ajpath.2021.07.008

Masayuki Shimoda, Yoko Endo + Show 9 more

Open Access

https://doi.org/10.1016/j.ajpath.2021.07.008

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Abstract

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.

Highlights

From the Departments of Pathophysiology for Locomotive and Neoplastic Diseases* and Medicine for Orthopaedics and Motor Organ,y Juntendo University Graduate School of Medicine, Tokyo; the Department of Pathology,z Keio University School of Medicine, Tokyo; and the Biological Science Research,x Kao
These data are the first to demonstrate that cartilage destruction and osteophyte formation are suppressed in HybidÀ/À mice and suggest that Hybid antibody (Hybid)-mediated HA depolymerization is implicated for the progression of mechanically-induced knee osteoarthritis
In the OA model developed by medial collateral ligament transection with meniscus removal (MCLT/M OA model), this study demonstrated that compared with wild-type mice, destruction of articular cartilage and osteophyte formation are attenuated in HybidÀ/À mice, in which high-molecular-weight HA (HMW-HA) was accumulated in the joint tissues

Summary

Introduction

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 (HybidÀ/À) mice compared with wild-type 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 HybidÀ/À mice was observed in destabilization of the medial meniscus model. These data are the first to demonstrate that cartilage destruction and osteophyte formation are suppressed in HybidÀ/À mice and suggest that Hybid-mediated HA depolymerization is implicated for the progression of mechanically-induced knee osteoarthritis.

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