Schematic of the multi-scale modeling of OBs, OCs and MMs.

<p><b>Intracellular scale</b>: describes the communication among myeloma cells, osteoclasts and osteoblasts and their ‘phenotypic’ switches. <b>Intercellular scale</b>: describes the dynamics of molecules in signaling pathways for each cell after receiving cytokine stimulation from other cells and the specific migration rules for cells. <b>Tissue scale</b>: describes the diffusion of drugs and cytokines.</p

A comparison of the experimental and simulated data after BHQ880 treatment.

<p>A comparison of the experimental and simulated data after BHQ880 treatment.</p

3D snapshots of the tumor system with single-agent BHQ880 treatment at (a) time step 40, (b) time step 50 and (c) time step 120.

<p>3D snapshots of the tumor system with single-agent BHQ880 treatment at (a) time step 40, (b) time step 50 and (c) time step 120.</p

The effect of BHQ880 on the number of OBs, OCs and MMs.

<p>The effect of BHQ880 on the number of OBs, OCs and MMs.</p

The effect of GCs on the number of OBs, OCs and MMs.

<p>The effect of GCs on the number of OBs, OCs and MMs.</p

The effect of BHQ880 + GCs, BHQ880 + Lidamycin,GCs + Lidamycin, and BHQ880 + GCs + Lidamycin on the number of OBs, OCs and MMs.

<p>The effect of BHQ880 + GCs, BHQ880 + Lidamycin,GCs + Lidamycin, and BHQ880 + GCs + Lidamycin on the number of OBs, OCs and MMs.</p

The effects of BHQ880, GCs and Lidamycinon restoring the balance between OCs and OBs and killing MMs.

<p>The effects of BHQ880, GCs and Lidamycinon restoring the balance between OCs and OBs and killing MMs.</p

3D snapshots of the tumor system with single-agent GC treatment at (a) time step 60, (b) time step 65 and (c) time step 120.

<p>3D snapshots of the tumor system with single-agent GC treatment at (a) time step 60, (b) time step 65 and (c) time step 120.</p

The dynamics of OBs, OCs and MMs without drug treatment.

<p>The dynamics of OBs, OCs and MMs without drug treatment.</p

The signaling pathway for MMs, OBs and OCs.

<p><b>I</b>: The Wnt signaling pathway stimulates the growth, differentiation and activity of osteoblasts. <b>II:</b>Dickkopf (DKK1) inhibits the phosphorylation of beta-catenin to prevent its degradation. <b>III:</b> The ratio of OPG/RANKL is negatively related to the number of OCs. <b>IV:</b> TNFα stimulates the formation of MMs and induces stromal cells to secrete factors, such as RANKL, that drive OC formation.</p