Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis.

Tu, Manli; Yang, Mi; Yu, Nanxi; Zhen, Gehua; Wan, Mei; Liu, Wenlong; Ji, Baochao; Ma, Hairong et al. · Bone Res · 2019

basic_science · Level V

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Abstract

Osteoarthritis (OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective disease-modifying therapy. Here, we report that elevated cyclooxygenase-2 (COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis (RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA (STR/Ort) mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OA-associated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.