Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain / 中国骨伤

OBJECTIVE@#To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model.@*METHODS@#Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted.@*RESULTS@#In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05).@*CONCLUSION@#Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Curcumin inhibits advanced glycation end products-induced cell apoptosis and mitochondrial dysfunction via elevating PPARγ in chondrocyte / 中国药理学通报

Aim To explore the mechanism of the protective effect of curcumin on advanced glycation end products (AGEs)-induced chondrocyte apoptosis and mitochondrial dysfunction whether by elevating peroxisome proliferators-activated receptor-γ (PPARγ) or not.Methods The ratio of apoptotic cells was assayed by TUNEL;the mitochondrial membrane potential(△Ψm) was evaluated by Rhodamine-123 fluorescence.The ATP content was assayed by related kits.The activity of caspase-3 was detected by spectrophotometry.The expression of cytochrome C,Bax,and Bcl-2 was detected by Western blot.The PPARγ expression was determined by Western blot and real-time PCR;in addition,its activity was assayed by DNA-binding method.Results AGEs could induce chondrocyte apoptosis and up-regulate the levels of cytochrome C and caspase-3.Simultaneously,AGEs decreased the levels of △ Ψm and ATP production.Mitochondrial permeability conversion pore inhibitor cyclosporine A could significantly protect the cells from apoptosis.In addition,both PPARγ specific agonist pioglitazone and curcumin significantly inhibited AGEs-induced chondrocytes apoptosis and mitochondrial dysfunction.However,pretreatment with PPARγ specific inhibitor GW9662 (10 μ mol · L-1) could significantly antagonize the protective effect of curcumin on mitochondrial damage induced by AGEs.Curcumin could also significantly increase PPARγtranscriptional activity induced by AGEs,together with a significant induction of PPARγprotein and mRNA expression.Conclusion Curcumin could effectively protect AGEs-induced chondrocyte mitochondrial dysfunction by upregulating PPARγ,thus protecting chondrocytes from apoptosis.