Roles of monocarboxylate transporter subtypes in promotion and suppression of osteoclast differentiation and survival on bone
2019
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
osteoclastdifferentiation 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
osteoclastson the surface of dentin in a concentration-dependent manner. Additionally, macrophages and
osteoclastswere 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 knockdownin macrophages enhanced
osteoclastformation induced by
RANKL, Mct2
gene knockdownsuppressed that. Finally, Mct2
gene silencingin mature
osteoclastsdecreased their number and, thereby,
bone resorption. These results suggest that MCT1 is a negative regulator and MCT2 a positive regulator of
osteoclastdifferentiation, while MCT2 is required for
bone resorptionby
osteoclasts.
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