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.
Highlights
Arthritis is a joint disorder that affects one or more joints.Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common forms of arthritis
Because PGE2 stimulates bone formation without stimulating modifying effect by rescuing subchondral bone structure in osteoclast bone remodeling,[12] we examined whether COX-2 is genetically modified mice with RA, we gavage-fed the COX-2 elevated in subchondral bone formation in STR/Ort mice
We found that elevated levels of COX-2 stimulated aberrant subchondral bone formation in the development of OA
Summary
Arthritis is a joint disorder that affects one or more joints. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common forms of arthritis. 0.5%–1% of the population has RA, and small joints are affected more frequently than large joints.[3] RA is characterized by increased levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1, in the synovial joints.[4] Currently, arthritis treatment focuses on controlling the symptoms, especially pain; there is no satisfactory prevention or cure. The and analgesic effects; the potential role of COX-2 in the serum level of PGE2 in 4-month-old STR/Ort mice was twice as pathogenesis of OA and the role of its inhibitors as disease- high as that in CBA controls (Fig. 3e). A. 2 in osteocytes or treatment with a COX-2 inhibitor attenuated high level of COX-2 was associated with joint pain, as demoncartilage degeneration in spontaneous OA and TNF-α transgenic strated by a higher response rate exhibited by STR/Ort mice in the RA mice. These results indicate that elevated COX-2 expression in subchondral bone is associated with spontaneous OA but not traumatic OA of mechanically unstable
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