Platelet factor 4 induces bone loss by inhibiting the integrin α5-FAK-ERK pathway.

Autor: Li W; 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.; Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences, Beijing, China., Zhang Q; Department of Orthopedics, Beijing Hospital and National Center of Gerontology and Institute of Geriatrics Medicine, Chinese Academy of Medical Sciences, Beijing, China.; Department of Orthopedics, Beijing Eden Hospital, Beijing, China., Gu R; 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., Zeng L; 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., Liu H; The Central Laboratory, 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.
Jazyk: angličtina
Zdroj: Animal models and experimental medicine [Animal Model Exp Med] 2023 Dec; Vol. 6 (6), pp. 573-584. Date of Electronic Publication: 2023 Aug 11.
DOI: 10.1002/ame2.12342
Abstrakt: 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 enzyme-linked 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 integrin α5-focal adhesion kinase-extracellular signal-regulated kinase (ITGA5-FAK-ERK) pathway was inhibited due to PF4 supplementation.
Conclusions: PF4 may be attributed to OVX-induced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.
(© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)
Databáze: MEDLINE
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