tetano
Editor, Senior Moderator
Life Sci
. 2023 May 2;121750.
doi: 10.1016/j.lfs.2023.121750. Online ahead of print. Acute coronavirus infection triggers a TNF-dependent osteoporotic phenotype in mice
Celso M Queiroz-Junior[SUP] 1 [/SUP], Anna C P M Santos[SUP] 2 [/SUP], Matheus R Gonçalves[SUP] 2 [/SUP], Camila B Brito[SUP] 2 [/SUP], Breno Barrioni[SUP] 3 [/SUP], Pedro J Almeida[SUP] 4 [/SUP], Marcela H Gonçalves-Pereira[SUP] 5 [/SUP], Tarcília Silva[SUP] 6 [/SUP], Sicília R Oliveira[SUP] 6 [/SUP], Marivalda M Pereira[SUP] 7 [/SUP], Helton C Santiago[SUP] 5 [/SUP], Mauro M Teixeira[SUP] 5 [/SUP], Vivian V Costa[SUP] 8 [/SUP]
Affiliations
Aims: 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.
Main methods: 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).
Key findings: 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[SUP]+[/SUP] 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[SUP]-/-[/SUP] mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts.
Significance: Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.
Keywords: Bone resorption; Coronavirus; Covid-19; Femur; MHV.
. 2023 May 2;121750.
doi: 10.1016/j.lfs.2023.121750. Online ahead of print. Acute coronavirus infection triggers a TNF-dependent osteoporotic phenotype in mice
Celso M Queiroz-Junior[SUP] 1 [/SUP], Anna C P M Santos[SUP] 2 [/SUP], Matheus R Gonçalves[SUP] 2 [/SUP], Camila B Brito[SUP] 2 [/SUP], Breno Barrioni[SUP] 3 [/SUP], Pedro J Almeida[SUP] 4 [/SUP], Marcela H Gonçalves-Pereira[SUP] 5 [/SUP], Tarcília Silva[SUP] 6 [/SUP], Sicília R Oliveira[SUP] 6 [/SUP], Marivalda M Pereira[SUP] 7 [/SUP], Helton C Santiago[SUP] 5 [/SUP], Mauro M Teixeira[SUP] 5 [/SUP], Vivian V Costa[SUP] 8 [/SUP]
Affiliations
- PMID: 37142087
- DOI: 10.1016/j.lfs.2023.121750
Aims: 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.
Main methods: 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).
Key findings: 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[SUP]+[/SUP] 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[SUP]-/-[/SUP] mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts.
Significance: Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.
Keywords: Bone resorption; Coronavirus; Covid-19; Femur; MHV.