Objective. To determine whether oral glucosamine alleviates cartilage degradation in an animal model of osteoarthritis (OA).Methods. The effect of 8 weeks of daily oral glucosamine hydrochloride on degeneration of articular cartilage was evaluated in rabbits in which anterior cruciate ligament transection (ACLT) was performed to induce OA. Animals were treated with glucosamine (n ‫؍‬ 16) or a placebo (n ‫؍‬ 16) and necropsied at 11 weeks. Seven unoperated rabbits served as controls. The articular cartilage was evaluated macroscopically and histologically and analyzed for total type II collagen and glycosaminoglycan (GAG) content.Results. Histologic analysis revealed that loss of proteoglycan, based on Safranin O-fast green staining, was significantly reduced in the lateral tibial plateau cartilage of ACL-transected limbs in the glucosamine group compared with ACL-transected limbs in the placebo group, with a similar, but not significant, trend for the lateral femoral condylar cartilage. Likewise, macroscopic analysis of cartilage showed that the lateral tibial plateau alone had a significantly lower rate of disease in the glucosamine group, which was consistent with the results of the independent histologic assessment. However, no significant treatment effect was detected when composite histologic scores were analyzed. A significant reduction in GAG content was observed in the femoral condyles of placebo-treated ACL-transected joints, but not in the same region of glucosamine-treated ACLtransected joints, compared with their respective contralateral unoperated joints.Conclusion. Oral administration of glucosamine had a detectable, site-specific, partial disease-modifying effect in this model of OA. From a clinical perspective, the administration of glucosamine did not prevent fibrillation and/or erosions of the articular cartilage in all of the treated animals, and no effects were detected in the medial joint compartments.In addition to decreasing pain, an ideal therapeutic agent for osteoarthritis (OA) would also prevent or retard the progression of established OA by reducing or, preferably, reversing the underlying pathologic processes (structure modifying), resulting in the retention or restoration of more normal articular cartilage function. The most common pharmacologic therapeutic agents currently used for OA are primarily palliative and include acetaminophen, nonsteroidal antiinflammatory drugs, corticosteroids, and hyaluronic acid (1,2). None of these drugs for OA are disease modifying.Analyses of many randomized clinical trials of oral glucosamine in OA patients support the contention that glucosamine is a symptom-modifying agent in OA (3-5), while investigators in many other trials have

The pathogenesis of septicemia can be triggered by LPS, a potent stimulus for PG synthesis. The enzyme cyclooxygenase (COX) is a rate-limiting step in PG production. COX exists as two isoforms: COX-1, which is constitutively expressed in most cell types, and COX-2, which is inducible by LPS and cytokines in a variety of cells. In this study we determined the role of the proinflammatory cytokines IL-1β and TNF-α released by LPS-stimulated U937 human macrophages in the regulation of COX-2. Macrophages exposed to LPS showed a rapid and sustained expression of COX-2 mRNA and protein for up to 48 h, whereas PGE2 production was notably enhanced only after 12 h. LPS increased COX-2 gene transcription and activation of the transcription factor NF-κB in a transient manner. LPS-treated macrophages produced high levels of TNF-α and moderate amounts of IL-1β protein. However, neutralizing Abs against these cytokines had no effect on COX-2 mRNA and protein expression, nor did they affect the stability of COX-2 mRNA. Interestingly, in the presence of LPS or exogenous IL-1β, COX-2 transcripts were stabilized, and actinomycin D inhibited their degradation. Only when LPS or IL-1β was removed did COX-2 mRNA decay with a t1/2 of ≥5 h. In contrast, dexamethasone promoted a faster decay of the LPS-induced COX-2 transcripts (t1/2 = 2.5 h). These results clearly demonstrate that LPS can regulate COX-2 at both transcriptional and posttranscriptional levels independently from endogenous IL-1β and TNF-α in human macrophages.