Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and foun...Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.展开更多
Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in...Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.展开更多
To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irr...To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4 treated groups, the CFU S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT ( P <0.01 or P <0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.展开更多
基金supported by the National Natural Science Foundation of China,Nos.31730031,32130060the National Natural Science Foundation of China,No.31971276(to JH)+1 种基金the Natural Science Foundation of Jiangsu Province,No.BK20202013(to XG)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(Major Program),No.19KJA320005(to JH)。
文摘Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.
基金Beijing Natural Science Foundation,Grant/Award Number:L222145CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2019-I2M-5-038+2 种基金Clinical Medicine Plus X-Young Scholars Project,Peking Universitythe Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2023LCXQ017National Natural Science Foundation of China,Grant/Award Number:81700935。
文摘Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.
基金the National Natural ScienceFoundation(Serial No. 3 9870 92 6)
文摘To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4 treated groups, the CFU S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT ( P <0.01 or P <0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.
