<p>Chronic exposure to cadmium (Cd) has been linked to bone dysfunction, including osteomalacia and osteoporosis. Such dysfunction may result from indirect disturbances in calcium (Ca) and phosphorus metabolism due to Cd-induced nephrotoxicity, as well as from direct Cd accumulation in bone tissue. However, the mechanisms by which Cd is taken up by bone-derived cells such as osteoblasts remain unclear. Cd may enter cells via metal transporters, such as ZIP8, ZIP14, and DMT1, as well as Ca²⁺ channels, including voltage-gated Ca²⁺ channels, TRPV6, and TRPM7. In this study, we systematically analyzed Cd transport efficiency and the expression levels of candidate pathways using rat osteosarcoma-derived UMR-106 cells, rat liver-derived TRL1215 cells, and rat basophilic leukemia RBL-2H3 cells. Cd accumulation in UMR-106 cells was similar to that in TRL1215 cells but lower than that in RBL-2H3 cells, which exhibited the highest expression of ZIP8 and ZIP14. The uptake of Cd²⁺ and Mn²⁺ in UMR-106 cells was competitively inhibited by Mn²⁺ and Cd²⁺, respectively, a pattern characteristic of ZIP8- and ZIP14-mediated transport. Treatment with verapamil, an L-type Ca²⁺ channel inhibitor, significantly reduced Cd uptake in UMR-106 cells. Suppression of ZIP8, ZIP14, DMT1, Ca_V1.3 (a component of L-type Ca²⁺ channels), TRPV6, and TRPM7 expression via siRNA transfection also significantly reduced Cd uptake. However, the degree of reduction ranged from 15 to 35%, indicating that no single pathway makes a predominant contribution. These findings suggest that diverse pathways, encompassing metal transporters and Ca²⁺ channels, contribute to Cd uptake in UMR-106 cells, although no single pathway predominates.</p>