Background Triggering receptor expressed on myeloid cells (TREMs) are a family of cell surface receptors that play important roles in innate and adaptive immunity. Among then, TREM-2 has been extensively studied in the osteoclast differentiation and the essential role of TREM-2 in human osteoclastogenesis has been well established. However, much less has been known about the role of TREM-1 in human osteoclast differentiation.
Objectives In this study, we investigated the role of TREM-1 in human osteoclast differentiation.
Methods In vitro osteoclastogenesis assays were performed using osteoclast precursors from normal peripheral blood. Gene expressions were analyzed using real-time PCR.
Results Consistent with previous reports, TREM-2 expression was strongly increased during generation of human osteoclast precursors (pOCs). In contrast, TREM-1 expression was significantly decreased during generation of human pOCs. Stimulation of TREM-1 using agonistic TREM-1 antibody resulted in a significant suppression of RANKL-induced osteoclastogenesis, as evidenced by diminished formation of TRAP+ multinucleated cells. In addition, TREM-1 stimulation strongly suppressed RANKL-induced expression of osteoclast-related genes such as cathepsin K, integrin β3 and NFATc1. TREM-1 stimulation also down-regulated gene expression and cell surface expression of M-CSF receptor that is essential for osteoclast differentiation and survival.
Conclusions In this study, we demonstrated that TREM-1 play a negative regulator in human osteoclast differentiation and our findings identify a new mechanism of negative regulation of osteoclastogenesis that play a role during inflammation.
Disclosure of Interest None Declared
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