LPS-Mediated Transcriptional Changes in Myeloid Lineage Cells: Macrophages and Osteoclasts

This bone-resorptive activity is mediated by osteoclasts (OCs), which differentiate from macrophages upon exposure to RANKL. While the non-autonomous effects of the inflammasome on the osteoclast lineage are well characterized, its cell-intrinsic (autonomous) role within these cells remains poorly understood.

To address this knowledge gap, we treated mouse bone marrow-derived macrophages (BMDMs) with RANKL and monitored NLRP3 expression during osteoclastogenesis. Surprisingly, NLRP3 expression progressively declined as cells differentiated into osteoclasts, but was restored upon LPS priming. When OC cultures were exposed to LPS followed by nigericin to assess NLRP3 inflammasome activation, we observed robust inflammasome assembly in undifferentiated BMDMs, as expected.