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Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model.

ABSTRACT: Fractures still present a significant burden to patients due to pain and periods of unproductivity. Numerous growth factors have been identified to regulate bone remodeling. However, to date, only the bone morphogenetic proteins (BMPs) are used to enhance fracture healing in clinical settings. Activins are pleiotropic growth factors belonging to the TGF-? superfamily. We and others have recently shown that treatment with recombinant fusion proteins of activin receptors greatly increases bone mass in different animal models by trapping activins and other ligands thus inhibiting their signaling pathways. However, their effects on fracture healing are less known. Twelve-week old male C57Bl mice were subjected to a standardized, closed tibial fracture model. Animals were divided into control and treatment groups and were administered either PBS control or a soluble activin type IIB receptor (ActRIIB-Fc) intraperitoneally once a week for a duration of two or four weeks. There were no significant differences between the groups at two weeks but we observed a significant increase in callus mineralization in ActRIIB-Fc-treated animals by microcomputed tomography imaging at four weeks. Bone volume per tissue volume was 60%, trabecular number 55% and bone mineral density 60% higher in the 4-week calluses of the ActRIIB-Fc-treated mice (p<0.05 in all). Biomechanical strength of 4-week calluses was also significantly improved by ActRIIB-Fc treatment as stiffness increased by 64% and maximum force by 45% (p<0.05) compared to the PBS-injected controls. These results demonstrate that ActRIIB-Fc treatment significantly improves healing of closed long bone fractures. Our findings support the previous reports of activin receptors increasing bone mass but also demonstrate a novel approach for using ActRIIB-Fc to enhance fracture healing.

SUBMITTER: Puolakkainen T

PROVIDER: S-EPMC5509431 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model.

Puolakkainen Tero T Rummukainen Petri P Lehto Jemina J Ritvos Olli O Hiltunen Ari A Säämänen Anna-Marja AM Kiviranta Riku R

PloS one 20170713 7

Fractures still present a significant burden to patients due to pain and periods of unproductivity. Numerous growth factors have been identified to regulate bone remodeling. However, to date, only the bone morphogenetic proteins (BMPs) are used to enhance fracture healing in clinical settings. Activins are pleiotropic growth factors belonging to the TGF-β superfamily. We and others have recently shown that treatment with recombinant fusion proteins of activin receptors greatly increases bone mas ...[more]

PMID: 28704409

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Project description:Introduction and importance: Unicondylar tibial plateau fractures with tibial shaft fractures are extremely rare among the elderly group of people. The traditional treatment method is to apply double plates to fix unicondylar tibial plateau fractures combined with tibial shaft fractures respectively, but this fixation method can disrupt the blood supply around the soft tissues and increase the rate of postoperative infection and fracture non-union. In this paper, we would analyse an old unicondylar tibial plateau fracture (Schatzker type III) with tibial shaft fracture which admitted to our department and discussed the efficacy of using intramedullary nails and plates in the treatment of these fractures. Case presentation A 78-year-old woman with an old unicondylar tibial plateau fracture combined with tibial shaft fracture was presented in this case. Using an intramedullary nail combined with a plate to achieve good results. Clinical discussion This case represents a rare case of an unicondylar tibial plateau fracture with a tibial shaft fracture. In this case, the tibial plateau fracture was first incised and internally fixed with a 9-hole plate across the fracture line of the tibial shaft, followed by fixing the tibial shaft fracture with an intramedullary nail. This treatment helped us successfully reset the unicondylar tibial plateau fracture with tibial shaft fracture and provided a satisfactory outcome for the patient. Conclusion Using intramedullary nails combined with plates to treat unicondylar tibial plateau fractures with tibial shaft fractures allowed for a predictable healing result. Highlights • Unicondylar tibial plateau fractures with tibial shaft fractures are extremely rare in the elderly.• Traditional double plate internal fixation seriously affected soft tissue and bone healing.• The use of plates in combination with intramedullary nails can reduce the destruction of soft tissue and fix both the tibial plateau and the tibial shaft.

Dataset Information

Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model.

Publications

Soluble activin type IIB receptor improves fracture healing in a closed tibial fracture mouse model.

Similar Datasets

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