Patients with multiple myeloma (MM) often develop myeloma bone disease (MBD). The development of MBD from MM is considered to be caused by an abnormal bone marrow microenvironment. Macrophage inhibitory cytokine-1 (MIC-1) is a member of the transforming growth factor‑β superfamily. In patients with MM, MIC‑1 is expressed at high levels, however, whether this increased expression of MIC‑1 is associated with the development of MBD from MM remains to be elucidated. The present study investigated whether MIC‑1 is essential for the osteoclastic differentiation of peripheral blood mononuclear cells (PBMNCs) by using a co‑culture system, in which the PBMNCs were co‑cultured with RPMI‑8226 cells. The expression of MIC‑1 in the RPMI‑8226 cells was knocked down using RNA interference. Osteoclastic differentiation was evaluated using tartrate‑resistant acid phosphatase staining and lacunar resorption on dentine slices. The expression of receptor activator of nuclear factor‑κB ligand (RANKL) and phosphorylation of extracellular signal‑regulated kinase (Erk)1/2 were measured using Western blotting. It was found that the reduced expression of MIC‑1 in the RPMI‑8226 cells inhibited the osteoclastic differentiation of PBMNCs and decreased the expression levels of RANKL and phosphorylated Erk1/2. It was concluded that MIC‑1 promoted the osteoclastic differentiation of PBMNCs via the RANKL‑Erk1/2 signaling pathway and, therefore, MIC‑1 may offer potential as a target in the design of strategies to treat MBD.