Lower Macroscopic Scores Research Articles

Protective Effect of Diet-Supplemented and Endogenously Produced Omega-3 Fatty Acids against HFD-Induced Colon Inflammation in Mice.

Perilla (Perilla frutescens) oil reduces high-fat-diet-induced colon inflammation by suppressing the NF-κB pathway. In the current study, we compared the effect of endogenously produced and externally supplemented omega-3 fatty acids on high-fat-diet-induced colon inflammation. The fat-1 transgenic mice that endogenously synthesize omega-3 fatty acids were backcrossed with C57BL/6J wild-type mice to obtain transgenic (TR) and wild-type (WT) littermates. Five-week-old male littermates were divided into five groups: two groups fed 10% normal diet (WTLD, TRLD) and three groups fed with a 60% fat high-fat diet (WTHD, TRHD, and WTPO). In the WTPO group, 8% (w/w) of perilla oil was added. Perilla oil supplemented WT mice and fat-1 transgenic mice suppressed high-fat-diet-induced body weight and improved serum lipid levels. Furthermore, the WTPO and TRHD groups exhibited increased colon length, lower macroscopic scores, and reduced levels of pro-inflammatory markers and improved epithelial integrity barrier markers. The expression of GPR120 was increased in the WTPO group. Altogether, our results indicated that perilla oil could improve the symptoms of colon inflammation as an alternate omega-3 fatty acid supplement.

The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis

BackgroundMIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA).MethodsStarting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n = 7/group) for 7 weeks. The four treatment groups were: (1) sham + vehicle; (2) ACLT + vehicle; (3) ACLT + MIV-711, 30 µmol/kg and (4) ACLT + MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n = 15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured.ResultsIn ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p < 0.001) and CTX-II levels by up to 74% (p < 0.001) compared to ACLT vehicle controls. ACLT surgery significantly reduced the total thickness of the subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p < 0.001) and 80% (p < 0.001), respectively. Synovial CTX-II levels were reduced by 55–57% (p < 0.001) compared to baseline. MIV-711-treated animals had 25–37% lower macroscopic scores in the femur condyles and 13–33% lower macroscopic scores in the tibial plateaus.ConclusionsMIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.