Biros, Erik, Malabu, Usman H., Vangaveti, Venkat N., Birosova, Eva, and Moran, Corey S. (2022) The IFN-γ/miniTrpRS signaling axis: an insight into the pathophysiology of osteoporosis and therapeutic potential. Cytokine & Growth Factor Reviews, 64. pp. 7-11.

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Abstract

Osteoporosis results from dysregulated bone remodeling with increased osteoclast-mediated destruction of bones. We have recently shown in vitro the truncated tryptophanyl-tRNA synthetase (mini-TrpRS)-dependent action of interferon-gamma (IFN-γ) to promote myeloid lineage multinucleation, a fundamental step in the osteoclast formation. In particular, we found that IFN-γ readily induced monocyte aggregation leading to multinuclear giant cell formation that paralleled marked upregulation of mini-TrpRS. However, blockade of mini-TrpRS with its cognate amino acid and decoy substrate D-Tryptophan prevented mini-TrpRS signaling, and markedly reduced the aggregation of monocytes and multinucleation in the presence of IFN. The cell signaling mechanism executed by mini-TrpRS appears inevitably in any inflammatory environment that involves IFN-γ with outcomes depending on the cell type involved. Here, we elaborate on these findings and discuss the potential role of the IFN-γ/mini-TrpRS signaling axis in osteoporosis pathophysiology, which may eventually materialize in a novel therapeutic perspective for this disease.

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