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Monocarboxylate transporters (MCTs) provide transmembrane transport of monocarboxylates such as lactate and pyruvate. The present results showed that α-cyano-4-hydroxycinnamic acid (CHC), an inhibitor of MCTs, promoted osteoclast differentiation from macrophages at lower concentrations (0.1–0.3 mM) and suppressed that at a higher concentration (1.0 mM). On the other hand, CHC reduced the number of mature osteoclasts on the surface of dentin in a concentration-dependent manner. Additionally, macrophages and osteoclasts were found to express the  Mct1 ,  Mct2 , and  Mct4  genes, with  Mct1  and  Mct4  expression higher in macrophages, and that of  Mct2  higher in osteoclasts. Although  Mct1  gene knockdown in macrophages enhanced osteoclast formation induced by RANKL,  Mct2  gene knockdown suppressed that. Finally,  Mct2  gene silencing in mature osteoclasts decreased their number and, thereby, bone resorption. These results suggest that MCT1 is a negative regulator and MCT2 a positive regulator of osteoclast differentiation, while MCT2 is required for bone resorption by osteoclasts.

Roles of monocarboxylate transporter subtypes in promotion and suppression of osteoclast differentiation and survival on bone