Figure 3.

Schematic illustration depicting the intrinsic cell biology in GCTBs harboring H3.3G34W mutation. Telomere maintenance is worsened under the presence of the H3.3G34W variant through the hypomethylation of telomeric regions. The hTERT enzyme is also reactivated upon telomere shortening. On the other hand, H3.3G34W can increase the RANKL expressions on macrophages’ cell surface, which turns out to secrete more MCSF and recruit a larger amount of osteoclastic giant cells, leading to osteoclastogenesis. (Abbreviations: GCTBs—Giant Cell Tumor of Bone, hTERT—human Telomerase Reverse Transcriptase, RANKL—Receptor Activator of Nuclear Factor Kappa-B ligand, MCSF—Macrophage colony stimulation factor).