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Acute coronavirus infection triggers a TNF-dependent osteoporotic phenotype in mice

2023; Elsevier BV; Volume: 324; Linguagem: Inglês

10.1016/j.lfs.2023.121750

1879-0631

Celso Martins Queiroz‐Junior, Anna Clara Paiva Menezes dos Santos, Matheus Rodrigues Gonçalves, Camila Bernardo de Brito, Breno Rocha Barrioni, Pedro J. Almeida, Marcela Helena Gonçalves-Pereira, Tarcı́lia Aparecida Silva, Sicília Rezende Oliveira, Marivalda M. Pereira, Helton C. Santiago, Mauro Martins Teixeira, Vivian Vasconcelos Costa,

Biomarkers in Disease Mechanisms

Millions of people died during the COVID-19 pandemic, but the vast majority of infected individuals survived. Now, some consequences of the disease, known as long COVID, are been revealed. Although the respiratory system is the target of Sars-CoV-2, COVID-19 can influence other parts of the body, including bone. The aim of this work was to investigate the impact of acute coronavirus infection in bone metabolism.We evaluated RANKL/OPG levels in serum samples of patients with and without acute COVID-19. In vitro, the effects of coronavirus in osteoclasts and osteoblasts were investigated. In vivo, we evaluated the bone phenotype in a BSL2 mouse model of SARS-like disease induced by murine coronavirus (MHV-3).Patients with acute COVID-19 presented decreased OPG and increased RANKL/OPG ratio in the serum versus healthy individuals. In vitro, MHV-3 infected macrophages and osteoclasts, increasing their differentiation and TNF release. Oppositely, osteoblasts were not infected. In vivo, MHV-3 lung infection triggered bone resorption in the femur of mice, increasing the number of osteoclasts at 3dpi and decreasing at 5dpi. Indeed, apoptotic-caspase-3+ cells have been detected in the femur after infection as well as viral RNA. RANKL/OPG ratio and TNF levels also increased in the femur after infection. Accordingly, the bone phenotype of TNFRp55-/- mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts.Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.