Figure 3.

Pathological bone turnover. The presence of MM cells alters bone homoeostasis by cytokine production (e.g. IL-1β, RANKL, MIP-1α) that recruit and activate OC, increasing bone resorption. OC may also produce growth factors (IL-6) for MM cells, which may also secrete cytokines that suppress OB activity. The synergy between MM and OC confers them an advantage with respect to OB. The arrows indicate the net effects associated with pay-off matrix entries in equations (4.2) and (4.3). The invariance of the evolutionary dynamics under projective transformations (see main text for details) leads to the definition of the minimal pay-off matrix in equation (4.3), with parameters depicted inside circles, that accounts for all dynamical scenarios encompassing the coevolution of these three cell types.