Carvacrol Inhibits Osteoclastogenesis and Negatively Regulates the Survival of Mature Osteoclasts
Carvacrol Inhibits Osteoclastogenesis and Negatively Regulates the Survival of Mature Osteoclasts
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DOI：
10.1248/bpb.b16-00117
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发表时间：
2016-07-01
影响因子：
2
通讯作者：
Coetzee, Magdalena
中科院分区：
文献类型：
--
作者：
Deepak, Vishwa;Kasonga, Abe;Coetzee, Magdalena
骨是一种动态组织，在成骨细胞和破骨细胞的作用下不断重塑。破骨细胞活性在骨质疏松症和牙周炎期间升高，导致骨小梁和牙槽骨的过度损失。破骨细胞在对细胞因子产生核因子-κ B（NF-κ B）配体（RANKL）受体激活剂和细菌攻击脂多糖（LPS）的炎症反应中形成。香芹酚是一种存在于牛至和红花中的单萜酚，是一种具有已知药用特性的天然化合物。我们研究了香芹酚对RANKL和LPS诱导的破骨细胞形成的影响。香芹酚抑制RAW264.7巨噬细胞和人CD 14（+）单核细胞中RANKL诱导的抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞的形成。此外，香芹酚抑制LPS诱导的破骨细胞在RAW 264.7巨噬细胞中的形成。对潜在分子机制的研究表明，香芹酚以剂量依赖性方式下调RANKL诱导的NF-κ B活化。此外，NF-κ B活化的抑制与抑制κ B抑制剂（I κ B）激酶（IKK）活化和减弱NF-κ B抑制剂（I κ Ba）降解相关。香芹酚通过激活caspase-3和DNA片段化增强成熟破骨细胞的凋亡。此外，香芹酚不影响增殖的MC 3 T3-E1成骨细胞样细胞的活力。总的来说，这些结果表明香芹酚通过损害NF-κ B途径和诱导成熟破骨细胞凋亡来减轻破骨细胞生成。
Bone is a dynamic tissue that undergoes continuous remodeling coupled with the action of osteoblasts and osteoclasts. Osteoclast activity is elevated during osteoporosis and periodontitis resulting in excessive loss of trabecular and alveolar bone. Osteoclasts are formed in an inflammatory response to cytokine production receptor activator of nuclear factor-kappaB (NF-kappa B) ligand (RANKL) and bacterial challenge lipopolysaccharide (LPS). Carvacrol, a monoterpenic phenol present in Origanuin vulgare and Thymus vulgaris, is a natural compound with known medicinal properties. We investigated the effects of carvacrol on osteoclast formation induced by RANKL and LPS. Carvacrol suppressed RANKL-induced formation of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells in RAW264.7 macrophages and human CD14(+) monocytes. Furthermore, carvacrol inhibited LPS-induced osteoclast formation in RAW264.7 macrophages. Investigation of the underlying molecular mechanisms revealed that carvacrol downregulated RANKL-induced NF-kappa B activation in a dose-dependent manner. Furthermore, the suppression of NF-kappa B activation correlated with inhibition of inhibitor of kappaB (I kappa B) kinase (IKK) activation and attenuation of inhibitor of NF-kappa B (I kappa Ba) degradation. Carvacrol potentiated apoptosis in mature osteoclasts by caspase-3 activation and DNA fragmentation. Moreover, carvacrol did not affect the viability of proliferating MC3T3-E1 osteoblast-like cells. Collectively, these results demonstrate that carvacrol mitigates osteoclastogenesis by impairing the NF-kappa B pathway and induction of apoptosis in mature osteoclasts.