Figure 2.

Osteocyte role in MM bone disease. Bone destruction in MM rely up the exchange of soluble factors as well as the interactions between MM cells and OCLs and OBs. Osteocytes play a pivotal role in orchestrating this interplay. Cell-to cell interaction with MM cells, upregulates RANKL while downregulates OPG in osteoprogenitor cells, thus stimulating OCL survival. Under MM stimuli, osteocytes and OBs undergo apoptosis and autophagic cell death. In this scenario, osteocytes produce the pro-osteoclastogenic factors IL-11, CCL3, and MMP1 increasing OCL activity. The physical contact between MM cells and osteocytes induce the reciprocal activation of Notch pathway resulting in increased expression of RANKL, which stimulates OCL, and Scl, which suppress bone formation by osteocytes as well as MM cells growth and osteocyte apoptosis. TNF-α produced by MM cells exacerbated these effects. The effects of MM cells on osteocytic expression of Scl is controversial since some authors reported that osteocytes isolated from tumor-bearing mice expressed lower Scl than non-tumor bearing mice. Moreover, MM cells induce the expression of Scl in OBs via secretion of Dkk-1. See text for details.