BoneKEy reports | 2014 | Casanova M, Schindeler A, Little D, Müller R
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Conflict of interest statement: The authors declare no conflict of interest. 9. Injury. 2021 Jun;52 Suppl 2:S44-S48. doi: 10.1016/j.injury.2020.11.051. Epub 2020 Nov 18. Experimental agents to improve fracture healing: utilizing the WNT signaling pathway. Haffner-Luntzer M(1). Author information: (1)Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany. Electronic address: melanie.haffner-luntzer@uni-ulm.de. The process of bone healing largely recapitulates bone development in the embryo and ideally achieves complete restoration of bone shape and structure. However, because successful fracture healing requires tight interactions of numerous cell types and signaling molecules, any disruption of this highly coordinated processes can result in delayed healing or even non-union formation. The rate of fracture healing complications in orthopedic patients is reported to be 5-20%. Therefore, there is a need for new therapeutic strategies to improve fracture healing in patients with healing complications. One treatment strategy would include the easy and safe application of a pharmacological agent inducing osteoanabolic effects during fracture healing. One potential promising molecular target is the osteoanabolic WNT signaling pathway. This pathway plays an important role during embryonic bone development, homeostasis, mechanotransduction, development of osteoporosis and bone regeneration. This review focuses on preclinical studies targeting WNT signaling molecules to accelerate fracture healing. The three main investigated antagonists of the WNT signaling pathway, which can be blocked experimentally by antibodies, are Sclerostin, Dickkopf-1 and Midkine. Treating animals with antibodies against these proteins enhanced bone formation in the fracture callus. This indicates a therapeutic potential for these antibodies to accelerate fracture healing in patients with orthopedic complications. Copyright © 2021 The Author. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.injury.2020.11.051
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