Gene expression changes are associated with severe bone loss and deficient fracture callus formation in rats with complete spinal cord injury.

Autor: Butezloff MM; School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Volpon JB; School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Ximenez JPB; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Astolpho K; School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Correlo VM; 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Braga, Portugal., Reis RL; 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Braga, Portugal., Silva RB; School of Dentistry of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Zamarioli A; School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. arianezamarioli@usp.br.
Jazyk: angličtina
Zdroj: Spinal cord [Spinal Cord] 2020 Mar; Vol. 58 (3), pp. 365-376. Date of Electronic Publication: 2019 Nov 07.
DOI: 10.1038/s41393-019-0377-y
Abstrakt: Study Design: Animal study.
Objectives: To investigate the effects of SCI on bone quality and callus formation.
Setting: University and hospital-based research center, Ribeirão Preto Medical School, Brazil.
Methods: Rats sustaining a complete SCI for 10 days received a fracture at the femoral diaphysis and were followed-up for 14 days. Bone callus and contralateral nonfractured tibia were assessed by DXA, µCT, ELISA, histomorphometry, immunohistochemistry, biomechanical test, and gene expression.
Results: SCI downregulated osteoblastic-related gene expression in the nonfractured tibias, associated with a twofold increase in osteoclasts and overexpression of RANK/RANKL, which resulted in lower bone mass, impaired microarchitecture, and weaker bones. On day 14 postfracture, we revealed early and increased trabecular formation in the callus of SCI rats, despite a marked 75% decrease in OPG-positive cells, and 41% decrease in density. Furthermore, these calluses showed higher porosity and thinner newly formed trabeculae, leading to lower strength and angle failure.
Conclusions: SCI-induced bone loss resulted from increased bone resorption and decreased bone formation. We also evidenced accelerated bone healing in the SCI rats, which may be attributed to the predominant intramembranous ossification. However, the newly formed bone was thinner, less dense, and more porous than those in the non-SCI rats. As a result, these calluses are weaker and tolerate lesser torsion deformation than the controls, which may result in recurrent fractures and characterizes a remarkable feature that may severely impair life quality.
Databáze: MEDLINE
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