{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:21:00Z","timestamp":1792156860743,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L222145"],"award-info":[{"award-number":["L222145"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700935"],"award-info":[{"award-number":["81700935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010triggered bone destruction in mice and determine the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 enzyme\u2010linked 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\u2010time polymerase chain reaction and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 integrin \u03b15\u2010focal adhesion kinase\u2010extracellular signal\u2010regulated kinase (ITGA5\u2010FAK\u2010ERK) pathway was inhibited due to PF4 supplementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PF4 may be attributed to OVX\u2010induced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5\u2010FAK\u2010ERK pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.12342","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T06:28:07Z","timestamp":1691735287000},"page":"573-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Platelet factor 4 induces bone loss by inhibiting the integrin\n                    <scp>\u03b15\u2010FAK\u2010ERK<\/scp>\n                    pathway"],"prefix":"10.1002","volume":"6","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology Peking University  Beijing China"},{"name":"Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Beijing Hospital and National Center of Gerontology and Institute of Geriatrics Medicine Chinese Academy of Medical Sciences  Beijing China"},{"name":"Department of Orthopedics Beijing Eden Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranli","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, National Health Commission Key Laboratory of Digital Technology of Stomatology Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical 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