In Silico Investigations of the Anti-Catabolic Effects of Pamidronate and Denosumab on Multiple Myeloma-Induced Bone Disease
Figure 2
The structure of the integrated models with pamidronate and denosumab.
Regulation mechanism 1: PTH stimulates RANKL expression on the surface of osteoblast precursors while inhibiting OPG secretion by active osteoblasts. Regulation mechanism 2: RANKL binds to RANK, which promotes differentiation of osteoclast precursors, while OPG inhibits the RANKL-RANK binding. Regulation mechanism 3: Bone resorption released TGF-β stimulates uncommitted osteoblast differentiation, inhibits osteoblast precursor differentiation and facilitates apoptosis of active osteoclasts. Regulation mechanism 4: MM cells adhere to BMSC, enabling IL-6 secretion by BMSC, RANKL expression on the surface of BMSC and MM-cell proliferation. Regulation mechanism 5: IL-6 facilitates MM-cell proliferation and stimulates RANKL expression on the surface of osteoblast precursors. Regulation mechanism 6: bone resorption released TGF-β stimulates IL-6 production by BMSC. Regulation mechanism 7: OPG is internalized and degraded by MM cells. Regulation mechanism 8: denosumab binds to RANKL to inhibit differentiation of osteoclast precursors. Regulation mechanism 9: pamidronate promotes the apoptosis of active osteoclasts. Regulation mechanism 10: pamidronate facilitates the apoptosis of MM cells. Regulation mechanism 11: NTX released from bone resorption is under the control of active osteoclasts.