Role for macrophage inflammatory protein (MIP)-1α and MIP-1β in the development of osteolytic lesions in multiple myeloma

摘要: Multiple myeloma (MM) cells cause devastating bone destruction by activating osteoclasts in the marrow milieu. However, mechanism of enhanced resorption patients with is poorly understood. In present study, we investigated a role C-C chemokines, macrophage inflammatory protein (MIP)–1α and MIP-1β, MM cell-induced osteolysis. These chemokines were produced secreted majority cell lines as well primary from patients. Secretion MIP-1α MIP-1β correlated ability to enhance osteoclastic both vitro vivo osteoclastogenic cultures rabbit cells, cocultures addition cell-conditioned media formation osteoclastlike pits an extent comparable effect recombinant MIP-1β. Importantly, these effects mostly reversed neutralizing antibodies against or their cognate receptor, CCR5, suggesting critical roles chemokines. We also demonstrated that stromal express CCR5 induce expression receptor activator nuclear factor-κB (RANK) ligand thereby stimulating osteoclast differentiation preosteoclastic cells. results suggest may be major osteoclast-activating factors