Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin

It is generally believed that bone micro-fractures, associated with osteocyte death, lead to osteoclast recruitment and thereupon to removal and replacement of damaged bone. However, the underlying mechanism is still incompletely defined. In this study we hypothesized that the pattern recognition receptor macrophage-inducible C-type lectin (Mincle) is expressed in osteoclasts and is responsible for the recognition of osteocyte death. To understand the mechanistic role of Mincle in osteoclasts, we performed in-depth analysis of the effect of Mincle deficiency on the genomic transcriptional network of osteoclasts. Whole transcriptome RNA sequencing (RNAseq) was performed on osteoclasts stimulated with necrotic osteocyte supernatant compared to control osteoclasts (stimulated with viable osteocyte supernatant), derived from either wildtype or Mincle knockout mice. In vitro differentiated osteoclasts from wildtype (WT, C57BL/6 mice) or Mincle knockout (KO, C57BL/6 background) mice were stimulated on day 1 of culture with either supernatant from viable osteocytes (control condition) or supernatant from necrotic osteocytes (generated by serum starvation) for 24h. The osteoclast RNA was extracted on day 3 of differentiation for RNA-seq.