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Viruses
Volume 17
Issue 2
10.3390/v17020143
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

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

by
Rosa Nicole Freiberger
1,†,
Cynthia Alicia Marcela López
1,†,
Patricio Jarmoluk
1,
María Belén Palma
2,3,
Cintia Cevallos
1,
Franco Agustin Sviercz
1,
Tomás Martín Grosso
1,
Marcela Nilda García
2,
Jorge Quarleri
1 and
M. Victoria Delpino
1,*
1
Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Laboratorio de Inmunopatología Viral, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina
2
Cátedra de Citología, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata 1900, Argentina
3
Laboratorio de Investigación Aplicada a Neurociencias (LIAN), Fleni, Consejo de Investigaciones Científicas y Técnicas (CONICET), Escobar 1625, Argentina
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this study.
Viruses 2025, 17(2), 143; https://doi.org/10.3390/v17020143
Submission received: 24 December 2024 / Revised: 10 January 2025 / Accepted: 21 January 2025 / Published: 22 January 2025
(This article belongs to the Special Issue Mechanism of Receptor Recognition in Coronavirus)
Versions Notes

Abstract

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.
Keywords: COVID-19; SARS-CoV-2; bone; osteoblasts COVID-19; SARS-CoV-2; bone; osteoblasts

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MDPI and ACS Style

Freiberger, R.N.; López, C.A.M.; Jarmoluk, P.; Palma, M.B.; Cevallos, C.; Sviercz, F.A.; Grosso, T.M.; García, M.N.; Quarleri, J.; Delpino, M.V. SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation. Viruses 2025, 17, 143. https://doi.org/10.3390/v17020143

AMA Style

Freiberger RN, López CAM, Jarmoluk P, Palma MB, Cevallos C, Sviercz FA, Grosso TM, García MN, Quarleri J, Delpino MV. SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation. Viruses. 2025; 17(2):143. https://doi.org/10.3390/v17020143

Chicago/Turabian Style

Freiberger, Rosa Nicole, Cynthia Alicia Marcela López, Patricio Jarmoluk, María Belén Palma, Cintia Cevallos, Franco Agustin Sviercz, Tomás Martín Grosso, Marcela Nilda García, Jorge Quarleri, and M. Victoria Delpino. 2025. "SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation" Viruses 17, no. 2: 143. https://doi.org/10.3390/v17020143

APA Style

Freiberger, R. N., López, C. A. M., Jarmoluk, P., Palma, M. B., Cevallos, C., Sviercz, F. A., Grosso, T. M., García, M. N., Quarleri, J., & Delpino, M. V. (2025). SARS-CoV-2 Impairs Osteoblast Differentiation Through Spike Glycoprotein and Cytokine Dysregulation. Viruses, 17(2), 143. https://doi.org/10.3390/v17020143

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