The Effect of a Cyclooxygenase 2 Inhibitor on Early Degenerated Human Nucleus Pulposus Explants

摘要

Study Design Preclinical in vitro culture of human degenerated nucleus pulposus (NP) tissue. Objective Cyclooxygenase 2 inhibitors (e.g., celecoxib) inhibit prostaglandin E₂ (PGE₂) production, and they have been shown to upregulate regeneration of articular cartilage. In this study, we developed an explant culture system for use with human tissue and tested the potential of celecoxib. Methods NP explants were cultured with or without 1 μM of celecoxib and were analyzed at days 0 and 7 for biochemical content (water, sulfated glycosaminoglycans, hydroxyproline, and DNA), gene expression (for disk matrix anabolic and catabolic markers), and PGE₂ content. Results Water and biochemical contents as well as gene expression remained close to native values after 1?week of culture. PGE₂ levels were not increased in freshly harvested human NP tissue and thus were not reduced in treated tissues. Although no anabolic effects were observed at the dosage and culture duration used, no detrimental effects were observed and some specimens did respond by lowering PGE₂. Conclusions Human degenerated NP explants were successfully cultured in a close to in vivo environment for 1 week. Further research, especially dosage-response studies, is needed to understand the role of PGE₂ in low back pain and the potential of celecoxib to treat painful disks. Keywords: explant culture, intervertebral disk degeneration, inflammation, cyclooxygenase 2 inhibitor, regenerative therapy