Short-Term Administration of HIV Protease Inhibitor Saquinavir Improves Skull Bone Healing with Enhanced Osteoclastogenesis.

Autor:	Liu H; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Shen Y; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Zhao B; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Poon EH; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Qi S; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Ker DFE; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Billiar TR; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Cooper GM; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Xu Y; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh., Wang D; From the Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University; the Institute for Tissue Engineering and Regenerative Medicine; the Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong; and the Departments of Surgery, Plastic Surgery, and Oral Biology and Bioengineering, University of Pittsburgh.
Jazyk:	angličtina
Zdroj:	Plastic and reconstructive surgery [Plast Reconstr Surg] 2022 Dec 01; Vol. 150 (6), pp. 1264e-1274e. Date of Electronic Publication: 2022 Sep 19.
DOI:	10.1097/PRS.0000000000009734
Abstrakt:	Background: Using immunomodulatory methods to address the challenging issue of craniofacial bone repair may be a potentially effective approach. The protease inhibitor saquinavir has been shown to inhibit the inflammatory response by targeting the toll-like receptor 4/myeloid differentiation primary response complex. Independently, inhibition of toll-like receptor 4 or myeloid differentiation primary response led to enhanced skull bone repair. Therefore, the authors aimed to investigate the effects of saquinavir on skull bone healing. Methods: The effects of saquinavir on skull bone healing were assessed by means of gene expression, histology, immunohistochemistry, and tomography in a mouse calvarial defect model. Subsequently, the role of saquinavir in cell viability, migration, and osteogenic and osteoclastogenic differentiation was also evaluated in vitro. Results: One-week saquinavir administration improved skull bone healing based on micro-computed tomographic and histomorphometric analyses. Compared to the vehicle control, 1-week saquinavir treatment (1) enhanced osteoclast infiltration (tartrate-resistant acid phosphatase staining) at day 7, but not at days 14 and 28; (2) induced more CD206 + M2 macrophage infiltration, but not F4/80 + M0 macrophages at days 7, 14, and 28; and (3) elevated osteoclastogenic gene RANKL (quantitative polymerase chain reaction) expression and other osteogenic and cytokine expression. Furthermore, in vitro data showed that saquinavir administration did not influence MC3T3-E1 cell migration or mineralization, whereas higher concentrations of saquinavir inhibited cell viability. Saquinavir treatment also enhanced the osteoclastic differentiation of bone marrow-derived precursors, and partially reversed high-mobility group box 1-driven osteoclastogenesis inhibition and elevated proinflammatory cytokine expression. Conclusion: The improved skull bone repair following short-term saquinavir treatment may involve enhanced osteoclastogenesis and modulated inflammatory response following skull injury. Clinical Relevance Statement: The authors' work demonstrates improved skull bone healing by short-term application of saquinavir, a drug traditionally used in the treatment of acquired immunodeficiency syndrome. As such, saquinavir may be repurposed for skeletal repair. (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.)
Databáze:	MEDLINE
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