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platelet factor 4 induces bone loss by inhibiting the integrinα5-FAK-ERK pathway

Animal Models and Experimental Medicine 2023年第6期6卷 573-584页

作者： Wei Li Qiwei Zhang Ranli Gu Lijun Zeng Hao Liu Department of Oral Pathology Peking University School and Hospital of StomatologyNational Center for StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing Key Laboratory of Digital StomatologyNational Health Commission Key Laboratory of Digital Technology of StomatologyPeking UniversityBeijingChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical SciencesBeijingChina Department of Orthopedics Beijing Hospital and National Center of Gerontology and Institute of Geriatrics MedicineChinese Academy of Medical SciencesBeijingChina Department of Orthopedics Beijing Eden HospitalBeijingChina Department of Prosthodontics Peking University School and Hospital of StomatologyNational Center for StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing Key Laboratory of Digital StomatologyNational Health Commission Key Laboratory of Digital Technology of StomatologyPeking UniversityBeijingChina The Central Laboratory Peking University School and Hospital of StomatologyNational Center for StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing Key Laboratory of Digital StomatologyNational Health Commission Key Laboratory of Digital Technology of StomatologyPeking UniversityBeijingChina

Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly ***,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying ***:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,*** differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red ***,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent *** bone microarchitecture of the femur was evaluated using microCT and histological ***,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western ***:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of ***,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to ***,in vivo mouse PF4 supplementation triggered bone deterioration of the *** 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 ***: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.

关键词： bone loss bone marrow mesenchymal stem cells integrinα5 osteogenesis platelet factor 4

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Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

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Neural Regeneration Research 2024年第1期19卷 190-195页

作者： Miao Gu Xiao Cheng Di Zhang Weiyan Wu Yi Cao Jianghong He Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina School of Basic Medical Sciences Hebei Key Laboratory of Nerve Injury and RepairChengde Medical UniversityChengdeHebei ProvinceChina

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and *** r,it is unclear what factors play a role in this *** this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve *** factor is an important molecule in cell apoptosis,diffe rentiation,survival,and ***,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after ***-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann *** 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 ***,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic *** findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon ***,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

关键词： axon elongation bioinformatic analysis cell migration cell proliferation dorsal root ganglia peripheral nerve regeneration peripheral nerve trauma platelet factor 4 rat sciatic nerve Schwann cells

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Effects of platelet factor 4 on Expression of Bone Marrow Heparan Sulfate in Syngenic Bone Marrow Transplantation Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2002年第3期22卷 190-192页

作者：孟凡凯孙汉英刘文励袁慧玲徐惠珍孙岚周银莉任天华 Department of Hematology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan

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 4 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.

关键词： platelet factor 4 bone marrow transplantation heparan sulfate

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