Rolipram, a phosphodiesterase 4 inhibitor, stimulates osteoclast formation by inducing TRANCE expression in mouse clavarial cells
Rolipram, a phosphodiesterase 4 inhibitor, stimulates osteoclast formation by inducing TRANCE expression in mouse clavarial cells
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咯利普兰 (Rolipram) 是一种磷酸二酯酶 4 抑制剂，通过诱导小鼠锁骨细胞中 TRANCE 表达来刺激破骨细胞形成
DOI：
10.1007/bf02975891
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发表时间：
2004-12-01
影响因子：
6.7
通讯作者：
Yim, MJ
中科院分区：
文献类型：
--
作者：
Cho, ES;Yu, JH;Yim, MJ
磷酸二酯酶（PDE）4是降解细胞内cAMP的酶。在本研究中，rolipram，一个特定的磷酸二酯酶（PDE）4抑制剂，对破骨细胞形成的影响进行了研究。咯利普兰诱导小鼠骨髓细胞和颅骨成骨细胞共培养中破骨细胞的形成。在没有颅骨成骨细胞的情况下没有观察到这种活性，表明颅骨成骨细胞可能是咯利普兰的靶细胞。通过加入骨保护素（OPG）完全阻断咯利普兰形成破骨细胞，OPG是破骨细胞分化因子、TNF相关活化诱导细胞因子（TRANCE，等同于RANKL、ODF和OPGL）的可溶性诱饵受体。北方印迹分析显示咯利普兰的作用与TRANCE mRNA在小鼠颅骨成骨细胞中的表达增加有关。总之，这些数据表明，PDE4抑制剂上调成骨细胞中TRANCE mRNA的表达，进而控制破骨细胞的形成。
Phosphodiesterase (PDE) 4 is an enzyme that degrades intracellular cAMP. In the present study, the effect of rolipram, a specific phosphodiesterase (PDE) 4 inhibitor, on osteoclast formation was investigated. Rolipram induced osteoclast formation in cocultures of mouse bone marrow cells and calvarial osteoblasts. This activity was not observed in the absence of calvarial osteoblasts, suggesting that calvarial osteoblasts are likely target cells of rolipram. Osteoclast formation by rolipram was completely blocked by the addition of osteoprotegerin (OPG), a soluble decoy receptor for the osteoclast differentiation factor, TNF-related activation-induced cytokine (TRANCE, identical to RANKL, ODF, and OPGL). Northern blot analysis revealed the effect of rolipram to be associated with the increased expression of TRANCE mRNA in mouse calvarial osteoblasts. Collectively, these data indicate that PDE4 inhibitor up-regulates the TRANCE mRNA expression in osteoblasts, which in turn controls osteoclast formation.