FIGURE 2.

Osteocyte apoptosis: key molecular mechanisms. A: scheme showing that proapoptotic stimuli activate death receptors in osteocytes and initiate caspase-3-mediated programmed cell death. Osteocytes adjacent to apoptotic osteocytes are thought to release proinflammatory and proosteoclastogenic cytokines that attract osteoclasts and promote local bone resorption. B: image showing TUNEL assay to detect degraded DNA in apoptotic osteocytes in paraffin-embedded bones infiltrated with myeloma cancer cells. C: image showing active caspase-3 immunostaining of paraffin-embedded human bone from an osteoporotic patient. Black arrows point to apoptotic osteocytes; red arrows point to healthy osteocytes. AGE, advanced glycation end-products; HMGB1, high mobility group box 1; ROS, reactive oxygen species; TNF, tumor necrosis factor-α; TRAIL, tumor necrosis factor-related apoptosis inducing ligand.