Figure 2.

The adaptor protein p62 may represent a viable target for the treatment of multiple myeloma bone disease (MMBD). (Left panel) Microcomputed tomography (μCT) and x-ray analysis of tibia injected with mouse 5TGM1-myeloma cells showing significant lytic bone destruction. Representative histological sections show infiltration of plasma cells in the marrow space and no evidence of new bone formation. (Right panel) A novel small molecule p62-ZZ domain antagonist XRK3F2 induced new periosteal woven bone formation and increased cortical bone. Interestingly, histological examination of the tibia shows evidence of new bone formation in areas adjacent to multiple myeloma (MM) cells. TRAP staining shows osteoclasts (OCs) and active bone remodeling in the newly formed bone. This suggests that the anabolic effects seen with XRK3F2 may require bone-resorbing OC activity allowing MM-exposed osteoblasts (OBs) to respond to OC-derived anabolic stimuli. Scale bars, 100 μ. (From Teramachi et al. 2016; adapted and modified, with permission, from Nature Publishing Group.)