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

Autor(es)

Butezloff, Mariana M. ^[1] ; Volpon, Jose B. ^[1] ; Ximenez, Joao P. B. ^[2] ; Astolpho, Kelly ^[1] ; Correlo, Vitor M. ^[3] ; Reis, Rui L. ^[3] ; Silva, Raquel B. ^[4] ; Zamarioli, Ariane ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Sao Paulo - Brazil

^[3] Univ Minho, Headquarters European Inst Excellence Tissue Engn, Biodegradables & Biomimet, 3Bs Res Grp Biomat Biodegradables & Biomimet, Braga - Portugal

^[4] Univ Sao Paulo, Sch Dent Ribeirao Preto, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SPINAL CORD; v. 58, n. 3, p. 365-376, MAR 2020.
• Citações Web of Science: 1

Resumo

Study design Animal study. Objectives To investigate the effects of SCI on bone quality and callus formation. Setting University and hospital-based research center, Ribeirao 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, mu CT, 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. (AU)

• Processo FAPESP: 15/22126-1 - Efeitos da lesão medular na qualidade da microarquitetura, resistência mecânica e metabolismo do tecido e calo ósseo de ratos paraplégicos. Serão os agentes farmacológicos, mecânicos e físicos capazes de melhorar a qualidade desses eventos biológicos?
• Beneficiário: Ariane Zamarioli
• Modalidade de apoio: Auxílio à Pesquisa - Regular