齐墩果酸对去卵巢诱导骨质疏松大鼠具有护骨作用，并能体外刺激骨髓间充质干细胞的成骨分化。
Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro.
机构信息
Department of Orthopaedics and Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
Menopause. 2012 Feb;19(2):225-33. doi: 10.1097/gme.0b013e3182272ef1.
OBJECTIVE
Oleanolic acid (OA) and its glycosides have been reported to prevent bone loss by inhibiting the formation of osteoclasts. However, because bone formation and resorption are balanced processes in bone metabolism, no studies have described the effect of OA on osteogenesis. The aim of the present study was to evaluate the osteoprotective effect of OA in rats with ovariectomy (OVX)-induced osteoporosis and to search for the molecular targets of OA in bone mesenchymal stem cells (bMSCs).
METHODS
Two-month-old female mice that underwent OVX were treated with OA (20 mg/kg a day). After 2 weeks and after 3 months, bone mass was evaluated by micro-CT, morphometry, and immunohistochemical detection. In addition, the expression of 256 genes was measured via microarray and confirmed by real-time reverse transcription-polymerase chain reaction. The effects of OA on the activities of bMSCs were also observed in vitro using alkaline phosphatase and cell proliferation assays.
RESULTS
Micro-CT displayed only a tendency for bone loss at 2 weeks but a decrease in bone mass at 3 months after OVX. OA treatment increased osteoblast number, increasing osteocalcin and runt-related protein 2 protein levels in vivo and facilitating the osteoblastic differentiation of bMSCs in vitro at doses of 10(-6) and 10(-5) M. Gene expression profile analysis revealed that OVX caused a marked dysregulation of gene expression, especially at 2 weeks, some of which was rescued by OA. Few of these genes overlapped, but their functions were involved in the Notch signaling pathway between two phases of the osteoporotic process.
CONCLUSIONS
OA exerts an osteoprotective effect in OVX-induced osteoporotic rats and stimulates the osteoblastic differentiation of bMSCs in vitro. The molecular mechanism of this effect might be related to the Notch signaling pathway and requires further investigation.
目的
齐墩果酸（OA）及其糖苷已被报道通过抑制破骨细胞的形成来预防骨质流失。然而，由于骨形成和吸收是骨代谢中的平衡过程，因此尚无研究描述 OA 对成骨的影响。本研究旨在评估 OA 对去卵巢（OVX）诱导的骨质疏松症大鼠的护骨作用，并寻找 OA 在骨髓间充质干细胞（bMSC）中的分子靶点。
方法
对 2 个月大的雌性去卵巢小鼠进行 OA（每天 20mg/kg）治疗。在 2 周和 3 个月后，通过 micro-CT、形态计量学和免疫组织化学检测评估骨量。此外，通过微阵列测量了 256 个基因的表达，并通过实时逆转录-聚合酶链反应进行了确认。还通过碱性磷酸酶和细胞增殖测定观察了 OA 对 bMSC 活性的体外影响。
结果
micro-CT 仅显示去卵巢后 2 周时骨丢失的趋势，但 3 个月时骨量减少。OA 治疗增加了成骨细胞数量，增加了体内骨钙素和 runt 相关蛋白 2 蛋白水平，并在 10（-6）和 10（-5）M 剂量下促进了 bMSC 的成骨分化。基因表达谱分析显示，OVX 导致基因表达明显失调，尤其是在 2 周时，其中一些被 OA 挽救。这些基因很少重叠，但它们的功能涉及骨质疏松症过程的两个阶段之间的 Notch 信号通路。
结论
OA 对去卵巢诱导的骨质疏松症大鼠具有护骨作用，并刺激 bMSC 的体外成骨分化。这种作用的分子机制可能与 Notch 信号通路有关，需要进一步研究。
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