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. 2011 Nov 8;6(11):e27494. doi: 10.1371/journal.pone.0027494

Figure 2. Schematic of the positive feedback cycles in the MM-bone model.

Figure 2

The positive feedback loop A forms the first cycle within the bone microenvironment, which is enhanced by the increased IL-6 concentrations due to MM-BMSC adhesion. IL-6 secreted by BMSC stimulates elevated RANKL expression on the surface of osteoblast precursors and further increased active osteoclasts, leading to bone resorption and TGF-β released from bone resorption. Released TGF-β, in turn, stimulates more IL-6 secretion by BMSC. The positive feedback loop B forms the second cycle. Simultaneous stimulation of MM-BMSC adhesion and TGF-β induces substantial IL-6 secretion by BMSC, which (together with MM-BMSC adhesion) causes MM-cell proliferation and further enhanced MM-BMSC adhesion. The first and the second cycle interact with each other by enhancing IL-6 production. Two regulations, MM-BMSC adhesion stimulating RANKL expression on the surface of BMSC and MM-cell degrading OPG, enhance the positive feedback cycles of MM-bone interactions through increasing IL-6 concentrations.