Ameloblastin and enamelin prevent osteoclast formation by suppressing RANKL expression via MAPK signaling pathway
Ameloblastin and enamelin prevent osteoclast formation by suppressing RANKL expression via MAPK signaling pathway
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DOI：
10.1016/j.bbrc.2017.01.181
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发表时间：
2017-04-08
影响因子：
3.1
通讯作者：
Nishihara, Tatsuji
中科院分区：
文献类型：
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作者：
Chaweewannakorn, Wichida;Ariyoshi, Wataru;Nishihara, Tatsuji
成釉蛋白(AmBN)和釉质蛋白(Enam)在釉质矿化过程中起着关键作用。以往的研究表明，这些釉质相关基因产物也影响骨的生长和改建；然而，其潜在的机制尚未阐明。在本研究中，我们观察了AMBN和ENAM对1，25-二羟基维生素D-3(1，25(OH)(2)D-3)和地塞米松(DEX)诱导的小鼠骨髓基质细胞株ST2细胞核因子kappaB受体激活物配体(RANKL)表达的影响。然后，我们验证了AMBN和ENAM对破骨细胞形成的影响。结果表明，重组人AMBN和重组人Enam可显著抑制1，25(OH)2D3和地塞米松诱导的RANKL基因和蛋白表达。有趣的是，rhAmbn和rhEnam减弱了1，25(OH)2D3和DEX刺激的ST2细胞中丝裂原活化蛋白激酶(MAPK)的磷酸化，包括ERK1/2、JNK和p38。此外，用ERK1/2和p38的特异性抑制剂，而不是JNK，可阻断RANKL的mRNA和蛋白的表达。细胞共培养结果显示，rhAmbn和rhEnam可下调1，25(OH)2D3和地塞米松刺激的ST2细胞诱导的小鼠骨髓细胞向破骨细胞的分化。这些结果提示AMBN和ENAM可能通过下调骨髓基质细胞p38和ERK1/2 MAPK信号通路间接抑制RANKL诱导的破骨细胞生成。(C)2017 Elsevier Inc.保留所有权利。
Ameloblastin (Ambn) and enamelin (Enam) play a pivotal role in enamel mineralization. Previous studies have demonstrated that these enamel-related gene products also affect bone growth and remodeling; however, the underlying mechanisms have not been elucidated. In the present study, we examined the effects of Ambn and Enam on the receptor activator of nuclear factor kappa-B ligand (RANKL) expression induced with 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and dexamethasone (DEX) on mouse bone marrow stromal cell line ST2 cells. We then verified the effect of Ambn and Enam on osteoclastogenesis. We found that pretreatment with recombinant human Ambn (rhAmbn) and recombinant human Enam (rhEnam) remarkably suppressed RANKL mRNA and protein expression induced with 1,25(OH)2D3 and DEX. Interestingly, rhAmbn and rhEnam attenuated the phosphorylation of mitogen-activated protein kinases (MAPK), including ERK1/2, JNK, and p38 in ST2 cells stimulated with 1,25(OH)2D3 and DEX. Moreover, pretreatment with specific inhibitors of ERK1/2 and p38, but not JNK, blocked RANKL mRNA and protein expression. Cell co-culture results showed that rhAmbn and rhEnam downregulated mouse bone marrow cell differentiation into osteoclasts induced with 1,25(OH)2D3 and DEX-stimulated ST2 cells. These results suggest that Ambn and Enam may indirectly suppress RANKL-induced osteoclastogenesis via downregulation of p38 and ERK1/2 MAPK signaling pathways in bone marrow stromal cells. (C) 2017 Elsevier Inc. All rights reserved.