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Background: Curcumin has anti-inflammatory effects. However, curcumin is poorly water-soluble, and when administered orally, formscurcumin conjugates with poor efficacy.Curcumin monoglucuronide (TBP1901) is highly water-soluble and can existinthe free-form in a greater proportion than curcumin in vivo. This study aimed to evaluate the effectiveness of intra-articular TBP1901 injections fora rat model of osteoarthritis (OA).Methods: Sixty-four male Wistar rats (12weeks old) that had receivedthe destabilized medial meniscus(DMM) surgery, were randomly separatedinto the TBP1901 injectionandthe saline solution injection (control) group. They were sacrificedat 1, 2, 6, or 10weeks postoperatively(n = 8 for each). The TBP1901 (30mg/mL) andsaline solutionof 50μLwere administered to the knee joint through the patella tendon twice a week for the rats sacrificedat1 and 2weeks or once a week for at6 and 10weeks. The OA changes were evaluated by micro-computed tomography (micro-CT), histology, and immunohistochemical analysis.Results:Curcumin fluorescence was confirmed in the articular cartilageand synovium of rats with TBP1901 injections at all observation periods.The TBP1901injections significantly reducedthe synovial inflammation at 1 and 2 weeks and the expression of TNFα in thetibialarticular cartilage at 6 weeks postoperatively.Moreover, TBP1901 injections ameliorated the articular cartilage structure, the subchondral bone (SB) plate thickness, and perforations from 6 to 10 weeks.As a result, there were significant differencesbetween groups in OA scores, SB plate thickness, and perforations at 10 weeks postoperatively.In addition, osteophyte formation in the TBP1901group was significantly suppressed after 10 weeks.Conclusion: This study reports the first evidence that TBP1901 injections suppress inflammation and osteophyte formation, and ameliorate the articular cartilage and SB pathologies by absorption in the articular cartilage and synovium in a rat DMM model.Therefore, intra-articular injections of TBP1901may be effective in improving OA pathology.

Background This study aimed to examine the effects of a single episode of in vivo cyclic loading on rat knee articular cartilage (AC) in mid-term observation and investigate relevant factors associated with the progression of post-traumatic osteoarthritis (PTOA). Methods Twelve-week-old Wistar rats underwent one episode of 60 cycles of dynamic compression of 20 N or 50 N on their right knee joint. The spatiotemporal changes in the AC after loading were evaluated using histology and immunohistochemistry at 3 days, 1, 2, 4 and 8 weeks after loading (n=6 for each condition). The chondrocyte vitality was assessed at 1, 3, 6 and 12 hours after loading (n=2 for each condition). ResultsA localized AC lesion on lateral femoral condyle was confirmed in all subjects. The surface and intermediate cartilage in the affected area degenerated after loading, yet the calcified cartilage remained intact. The expression of type II collagen in the lesion cartilage was upregulated after loading, whereas the superficial lubricin layer was eroded in response to cyclic compression. However, the distribution of superficial lubricin gradually recovered to the normal level 4 weeks after loading-induced injury.ConclusionWe confirmed that 60 times cyclic loading exceeding 20 N could result in cartilage damage in rat knee. Endogenous repairs in well-structured joints work well with rebuilding protective layers on the lesion cartilage surface, which could be the latent factor in delaying the progression of PTOA.