AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cart...AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect model.METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then assessed.RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.展开更多
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
基金Supported by Arteriocyte Inc.the Ohnell Family Foundationand Mr.and Mrs.Michael J Levitt
文摘AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect model.METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then assessed.RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.