Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis invivo and invitro
Curcumin alleviates glucocorticoid-induced osteoporosis by protecting osteoblasts from apoptosis invivo and invitro
复制标题
姜黄素通过保护成骨细胞免受体内和体外凋亡来减轻糖皮质激素诱导的骨质疏松症
DOI：
10.1111/1440-1681.12513
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发表时间：
2016-02-01
影响因子：
2.9
通讯作者：
Fu, Qin
中科院分区：
文献类型：
--
作者：
Chen, Zhiguang;Xue, Jinqi;Fu, Qin
姜黄素是姜黄（Curcumin longa L.）根茎中的活性成分，具有广泛的抗炎和抗癌特性。姜黄素以前被报道能够保护卵巢切除大鼠免受骨质疏松症。然而，姜黄素对糖皮质激素诱导的骨质疏松症（GIO）的影响尚不清楚。本研究探讨姜黄素对地塞米松（Dex）诱导的骨质疏松症及Dex诱导的成骨细胞凋亡的影响。用Dex皮下注射60天建立GIO大鼠模型，双能X线骨密度仪测定骨密度（BMD）明显降低。姜黄素100 mg/kg连续给药60天，可明显增加骨密度和骨碱性磷酸酶活性，减少羧基端胶原交联，增强骨机械强度，改善骨小梁微结构，从而减轻Dex诱导的骨质疏松。姜黄素在体内可明显逆转右旋糖酐诱导的股骨成骨细胞凋亡。在培养的原代成骨细胞中，姜黄素预处理浓度依赖性地减少了Dex诱导的凋亡成骨细胞的数量，下调Bax/Bcl-2的比例以及裂解的caspase-3和裂解的聚ADP-核糖聚合酶（PARP）的水平。此外，姜黄素预处理激活细胞外信号调节激酶（ERK）信号在右旋糖酐诱导成骨细胞上调p-ERK 1/2的表达水平。综上所述，我们的研究表明，姜黄素可以通过保护成骨细胞免于凋亡来改善GIO，这可能与ERK通路的激活有关。结果提示姜黄素可能是一种很有前途的防治GIO的药物。
Curcumin, an active component of the rhizomes of Curcumin longa L., possesses broad anti-inflammation and anti-cancer properties. Curcumin was previously reported to be capable of protecting ovariectomized rats against osteoporosis. However, the effect of curcumin on glucocorticoid-induced osteoporosis (GIO) is not yet clear. The present study investigated the effects of curcumin on dexamethasone (Dex)-induced osteoporosis invivo and Dex-induced osteoblast apoptosis invivo and invitro. The GIO rat model was induced by subcutaneous injection of Dex for 60days and verified to be successful as evidenced by the significantly decreased bone mineral density (BMD) determined using dual X-ray absorptiometry. Subsequently, curcumin administration (100mg/kg) for 60days obviously increased BMD and bone-alkaline phosphatase, decreased carboxy-terminal collagen cross links, enhanced bone mechanical strength, and improved trabecular microstructure, thereby alleviating Dex-induced osteoporosis. Mechanically, curcumin remarkably reversed Dex-induced femoral osteoblast apoptosis invivo. In cultured primary osteoblasts, pretreatment with curcumin concentration-dependently decreased the number of Dex-induced apoptotic osteoblasts by down-regulating the ratio of Bax/Bcl-2 as well as the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Moreover, curcumin pretreatment activated extracellular signal regulated kinase (ERK) signalling in Dex-induced osteoblasts by up-regulating the expression level of p-ERK1/2. Taken together, our study demonstrated that curcumin could ameliorate GIO by protecting osteoblasts from apoptosis, which was possibly related to the activation of the ERK pathway. The results suggest that curcumin may be a promising drug for prevention and treatment of GIO.