SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation

Autores
Freiberger, Rosa Nicole; López, Cynthia Alicia Marcela; Jarmoluk, Patricio; Palma, María Belén; Cevallos, Cintia; Sviercz, Franco Agustin; Grosso, Tomás Martín; García, Marcela Nilda; Quarleri, Jorge; Delpino, María Victoria
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Pulmonary and extrapulmonary manifestations have been reported following infection with SARS-CoV-2, the causative agent of COVID-19. The virus persists in multiple organs due to its tropism for various tissues, including the skeletal system. This study investigates the effects of SARS-CoV-2 infection, including both ancestral and Omicron viral strains, on differentiating mesenchymal stem cells (MSCs), the precursor cells, into osteoblasts. Although both viral strains can productively infect osteoblasts, precursor cell infection remained abortive. Viral exposure during osteoblast differentiation demonstrates that both variants inhibit mineral and organic matrix deposition. This is accompanied by reduced expression of runt-related transcription factor 2 (RUNX2) and increased levels of interleukin-6 (IL-6), a cytokine that negatively regulates osteoblast differentiation. Furthermore, the upregulation of receptor activator of nuclear factor kappa B ligand (RANKL) strongly suggests that the ancestral and Omicron variants may disrupt bone homeostasis by promoting osteoclast differentiation, ultimately leading to the formation of bone-resorbing cells. This process is dependent of spike glycoprotein since its neutralization significantly reduced the effect of infective SARS-CoV-2 and UV-C inactivated virus. This study underscores the capacity of ancestral and Omicron SARS-CoV-2 variants to disrupt osteoblast differentiation, a process essential for preserving the homeostasis and functionality of bone tissue.
Facultad de Ciencias Médicas
Materia
Ciencias Médicas
COVID-19
SARS-CoV-2
bone
osteoblasts
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/181449
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/181449
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine DysregulationFreiberger, Rosa NicoleLópez, Cynthia Alicia MarcelaJarmoluk, PatricioPalma, María BelénCevallos, CintiaSviercz, Franco AgustinGrosso, Tomás MartínGarcía, Marcela NildaQuarleri, JorgeDelpino, María VictoriaCiencias MédicasCOVID-19SARS-CoV-2boneosteoblastsPulmonary and extrapulmonary manifestations have been reported following infection with SARS-CoV-2, the causative agent of COVID-19. The virus persists in multiple organs due to its tropism for various tissues, including the skeletal system. This study investigates the effects of SARS-CoV-2 infection, including both ancestral and Omicron viral strains, on differentiating mesenchymal stem cells (MSCs), the precursor cells, into osteoblasts. Although both viral strains can productively infect osteoblasts, precursor cell infection remained abortive. Viral exposure during osteoblast differentiation demonstrates that both variants inhibit mineral and organic matrix deposition. This is accompanied by reduced expression of runt-related transcription factor 2 (RUNX2) and increased levels of interleukin-6 (IL-6), a cytokine that negatively regulates osteoblast differentiation. Furthermore, the upregulation of receptor activator of nuclear factor kappa B ligand (RANKL) strongly suggests that the ancestral and Omicron variants may disrupt bone homeostasis by promoting osteoclast differentiation, ultimately leading to the formation of bone-resorbing cells. This process is dependent of spike glycoprotein since its neutralization significantly reduced the effect of infective SARS-CoV-2 and UV-C inactivated virus. This study underscores the capacity of ancestral and Omicron SARS-CoV-2 variants to disrupt osteoblast differentiation, a process essential for preserving the homeostasis and functionality of bone tissue.Facultad de Ciencias Médicas2025-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/181449enginfo:eu-repo/semantics/altIdentifier/issn/1999-4915info:eu-repo/semantics/altIdentifier/doi/10.3390/v17020143info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:41:21Zoai:sedici.unlp.edu.ar:10915/181449Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:41:21.282SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
title SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
spellingShingle SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
Freiberger, Rosa Nicole
Ciencias Médicas
COVID-19
SARS-CoV-2
bone
osteoblasts
title_short SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
title_full SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
title_fullStr SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
title_full_unstemmed SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
title_sort SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation
dc.creator.none.fl_str_mv Freiberger, Rosa Nicole
López, Cynthia Alicia Marcela
Jarmoluk, Patricio
Palma, María Belén
Cevallos, Cintia
Sviercz, Franco Agustin
Grosso, Tomás Martín
García, Marcela Nilda
Quarleri, Jorge
Delpino, María Victoria
author Freiberger, Rosa Nicole
author_facet Freiberger, Rosa Nicole
López, Cynthia Alicia Marcela
Jarmoluk, Patricio
Palma, María Belén
Cevallos, Cintia
Sviercz, Franco Agustin
Grosso, Tomás Martín
García, Marcela Nilda
Quarleri, Jorge
Delpino, María Victoria
author_role author
author2 López, Cynthia Alicia Marcela
Jarmoluk, Patricio
Palma, María Belén
Cevallos, Cintia
Sviercz, Franco Agustin
Grosso, Tomás Martín
García, Marcela Nilda
Quarleri, Jorge
Delpino, María Victoria
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
COVID-19
SARS-CoV-2
bone
osteoblasts
topic Ciencias Médicas
COVID-19
SARS-CoV-2
bone
osteoblasts
dc.description.none.fl_txt_mv Pulmonary and extrapulmonary manifestations have been reported following infection with SARS-CoV-2, the causative agent of COVID-19. The virus persists in multiple organs due to its tropism for various tissues, including the skeletal system. This study investigates the effects of SARS-CoV-2 infection, including both ancestral and Omicron viral strains, on differentiating mesenchymal stem cells (MSCs), the precursor cells, into osteoblasts. Although both viral strains can productively infect osteoblasts, precursor cell infection remained abortive. Viral exposure during osteoblast differentiation demonstrates that both variants inhibit mineral and organic matrix deposition. This is accompanied by reduced expression of runt-related transcription factor 2 (RUNX2) and increased levels of interleukin-6 (IL-6), a cytokine that negatively regulates osteoblast differentiation. Furthermore, the upregulation of receptor activator of nuclear factor kappa B ligand (RANKL) strongly suggests that the ancestral and Omicron variants may disrupt bone homeostasis by promoting osteoclast differentiation, ultimately leading to the formation of bone-resorbing cells. This process is dependent of spike glycoprotein since its neutralization significantly reduced the effect of infective SARS-CoV-2 and UV-C inactivated virus. This study underscores the capacity of ancestral and Omicron SARS-CoV-2 variants to disrupt osteoblast differentiation, a process essential for preserving the homeostasis and functionality of bone tissue.
Facultad de Ciencias Médicas
description Pulmonary and extrapulmonary manifestations have been reported following infection with SARS-CoV-2, the causative agent of COVID-19. The virus persists in multiple organs due to its tropism for various tissues, including the skeletal system. This study investigates the effects of SARS-CoV-2 infection, including both ancestral and Omicron viral strains, on differentiating mesenchymal stem cells (MSCs), the precursor cells, into osteoblasts. Although both viral strains can productively infect osteoblasts, precursor cell infection remained abortive. Viral exposure during osteoblast differentiation demonstrates that both variants inhibit mineral and organic matrix deposition. This is accompanied by reduced expression of runt-related transcription factor 2 (RUNX2) and increased levels of interleukin-6 (IL-6), a cytokine that negatively regulates osteoblast differentiation. Furthermore, the upregulation of receptor activator of nuclear factor kappa B ligand (RANKL) strongly suggests that the ancestral and Omicron variants may disrupt bone homeostasis by promoting osteoclast differentiation, ultimately leading to the formation of bone-resorbing cells. This process is dependent of spike glycoprotein since its neutralization significantly reduced the effect of infective SARS-CoV-2 and UV-C inactivated virus. This study underscores the capacity of ancestral and Omicron SARS-CoV-2 variants to disrupt osteoblast differentiation, a process essential for preserving the homeostasis and functionality of bone tissue.
publishDate 2025
dc.date.none.fl_str_mv 2025-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/181449
url http://sedici.unlp.edu.ar/handle/10915/181449
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1999-4915
info:eu-repo/semantics/altIdentifier/doi/10.3390/v17020143
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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