Thrombopoietic agents enhance bone healing in mice, rats, and pigs.

Autor:	Childress PJ; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States.; Richard L. Roudebush VA Medical Center, Indianapolis, IN, 46202, United States., Nielsen JJ; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, United States.; Department of Chemistry, Purdue University, West Lafayette, IN, 47907, United States., Bemenderfer TB; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Dadwal UC; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States.; Richard L. Roudebush VA Medical Center, Indianapolis, IN, 46202, United States., Chakraborty N; Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States., Harris JS; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Bethel M; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Alvarez MB; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States.; Richard L. Roudebush VA Medical Center, Indianapolis, IN, 46202, United States., Tucker A; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Wessel AR; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Millikan PD; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Wilhite JH; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Engle A; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Brinker A; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Rytlewski JD; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Scofield DC; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Griffin KS; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Shelley WC; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Manikowski KJ; Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, 46222, United States., Jackson KL; Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, 46222, United States., Miller SA; Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States., Cheng YH; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Ghosh J; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Mulcrone PL; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States.; Richard L. Roudebush VA Medical Center, Indianapolis, IN, 46202, United States., Srour EF; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, United States.; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Yoder MC; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Natoli RM; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Shively KD; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Gautam A; Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States., Hammamieh R; Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, United States., Low SA; Department of Chemistry, Purdue University, West Lafayette, IN, 47907, United States., Low PS; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, United States.; Department of Chemistry, Purdue University, West Lafayette, IN, 47907, United States., McKinley TO; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Anglen JO; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States., Lowery JW; Division of Biomedical Science, Marian University College of Osteopathic Medicine, Indianapolis, IN, 46222, United States., Chu TG; Department of Biomedical and Applied Sciences, Indiana University School of Dentistry, Indianapolis, IN, 46202, United States., Kacena MA; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, United States.; Richard L. Roudebush VA Medical Center, Indianapolis, IN, 46202, United States.
Jazyk:	angličtina
Zdroj:	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2024 Dec 31; Vol. 40 (1), pp. 125-139.
DOI:	10.1093/jbmr/zjae191
Abstrakt:	Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration. Here we demonstrate the robust bone healing capabilities of the main megakaryocyte (MK) growth factor, thrombopoietin (TPO), and second-generation TPO agents using multiple animal models, including mice, rats, and pigs. This bone healing activity is shown in two fracture models (critical-sized defect [CSD] and closed fracture) and with local or systemic administration. Our transcriptomic analyses, cellular studies, and protein arrays demonstrate that TPO enhances multiple cellular processes important to fracture healing, particularly angiogenesis, which is required for bone union. Finally, the therapeutic potential of thrombopoietic agents is high since they are used in the clinic for other indications (eg, thrombocytopenia) with established safety profiles and act upon a narrowly defined population of cells. (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)
Databáze:	MEDLINE
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