IRF2 enhances RANKL-induced osteoclast differentiation via regulating NF-κB/NFATc1 signaling
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초록
Interferon regulatory factors (IRFs) play roles in various biologicalprocesses including cytokine signaling, cell growth regulationand hematopoietic development. Although it has beenreported that several IRFs are involved in bone metabolism,the role of IRF2 in bone cells has not been elucidated. Here,we investigated the involvement of IRF2 in RANKL-inducedosteoclast differentiation. IRF2 overexpression in osteoclast precursorcells enhanced osteoclast differentiation by regulatingthe expression of NFATc1, a master regulator of osteoclastogenesis. Conversely, IRF2 knockdown inhibited osteoclast differentiationand decreased the NFATc1 expression. Moreover, IRF2increased the translocation of NF-κB subunit p65 to the nucleusin response to RANKL and subsequently induced the expressionof NFATc1. IRF2 plays an important role in RANKL-inducedosteoclast differentiation by regulating NF-κB/NFATc1 signalingpathway. Taken together, we demonstrated the molecular mechanismof IRF2 in osteoclast differentiation, and provide a molecularbasis for potential therapeutic targets for the treatment ofbone diseases characterized by excessive bone resorption.
Abstract
Interferon regulatory factors (IRFs) play roles in various biologicalprocesses including cytokine signaling, cell growth regulationand hematopoietic development. Although it has beenreported that several IRFs are involved in bone metabolism,the role of IRF2 in bone cells has not been elucidated. Here,we investigated the involvement of IRF2 in RANKL-inducedosteoclast differentiation. IRF2 overexpression in osteoclast precursorcells enhanced osteoclast differentiation by regulatingthe expression of NFATc1, a master regulator of osteoclastogenesis. Conversely, IRF2 knockdown inhibited osteoclast differentiationand decreased the NFATc1 expression. Moreover, IRF2increased the translocation of NF-κB subunit p65 to the nucleusin response to RANKL and subsequently induced the expressionof NFATc1. IRF2 plays an important role in RANKL-inducedosteoclast differentiation by regulating NF-κB/NFATc1 signalingpathway. Taken together, we demonstrated the molecular mechanismof IRF2 in osteoclast differentiation, and provide a molecularbasis for potential therapeutic targets for the treatment ofbone diseases characterized by excessive bone resorption.
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