The abortive SARS‐CoV‐2 infection of osteoclast precursors promotes their differentiation into osteoclasts

SVIERCZ, FRANCO; JARMOLUK, PATRICIO; GODOY COTO, JOSHUA; CEVALLOS, CINTIA; FREIBERGER, ROSA NICOLE; LÓPEZ, CINTHYA ALICIA MARCELA; ENNIS, IRENE LUCIA; DELPINO, M. VICTORIA; QUARLERI, JORGE

JOURNAL OF MEDICAL VIROLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2024 vol. 96

0146-6615

The Coronavirus Disease 2019 (COVID‐19) pandemic has resulted in the loss ofmillions of lives, although a majority of those infected have managed to survive.Consequently, a set of outcomes, identified as long COVID, is now emerging. Whilethe primary target of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the respiratory system, the impact of COVID‐19 extends to various body parts,including the bone. This study aims to investigate the effects of acute SARS‐CoV‐2infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains.Monocyte‐derived macrophages, which serve as precursors to osteoclasts, wereexposed to both viral variants. However, the infection proved abortive, even thoughACE2 receptor expression increased postinfection, with no significant impact oncellular viability and redox balance. Both SARS‐CoV‐2 strains heightened osteoclastformation in a dose‐dependent manner, as well as CD51/61 expression and boneresorptive ability. Notably, SARS‐CoV‐2 induced early pro‐inflammatory M1macrophage polarization, shifting toward an M2‐like profile. Osteoclastogenesis‐related genes (RANK, NFATc1, DC‐STAMP, MMP9) were upregulated, andsurprisingly, SARS‐CoV‐2 variants promoted RANKL‐independent osteoclast formation.This thorough investigation illuminates the intricate interplay between SARS‐CoV‐2 and osteoclast precursors, suggesting potential implications for bonehomeostasis and opening new avenues for therapeutic exploration in COVID‐19.