Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, 1201, W University Dr., Edinburg, TX, 78539, USA.
Department of Biology, University of Texas Rio Grande Valley, 1201, W University Dr., Edinburg, TX, 78539, USA.
J Bone Miner Metab. 2019 Sep;37(5):780-795. doi: 10.1007/s00774-018-0983-3. Epub 2019 Feb 12.
In women, age-related bone loss is associated with increased risk of bone fracture. Existing therapies are associated with severe side effects; thus, there is a need to find alternative medicines with less or optimal side effects. Cissus quadrangularis (CQ), an Ayurvedic medicine used to enhance fracture healing, was tested for its bone protective properties and studied to discern the mechanism by which it is beneficial to bone. Female Sprague Dawley rats were either sham operated or ovariectomized and were fed CQ for 3 months. Several biochemical markers, cytokines and hormones were assayed. Femur, tibia and lumbar vertebrae were subjected to pQCT and µCT densitometry. MC3T3 cells were cultured, treated with CQ and used to analyze miRNA content and subjected to qPCR for gene expression analysis related to bone metabolism. CQO rats showed protected bone mass and microarchitecture of trabecular bone in the distal femoral metaphysis and the proximal tibial metaphysis. The lumbar vertebrae, however, showed no significant changes. Serum protein expression levels of P1NP increased and Trap5b and CTX levels decreased with in vivo CQ treatment. Some influence on the anti- and pro-inflammatory markers was also observed. Significantly high level of estradiol in the CQO rats was observed. In vitro expression of a few genes related to bone metabolism showed that osteocalcin increased significantly. The other genes-collagen I expression, SPP1, BMP2, DCAT1-decreased significantly. Certain miRNA that regulate bone turnover using the BMP pathway and Wnt signaling pathways were upregulated by CQ. qPCR after acute treatment with CQ showed significantly increased levels of osteocalcin and decreased levels of Wnt/β catenin antagonist DCAT1. Overall, CQ protected the microarchitecture of the long bones from ovariectomy-induced bone loss. This may be because of decreased inflammation and modulation through the BMP and Wnt signaling pathways. We conclude that CQ is a potential therapeutic agent to treat postmenopausal osteoporosis with no side effects.
在女性中，与年龄相关的骨质流失与骨折风险增加有关。现有的治疗方法与严重的副作用有关；因此，需要寻找副作用较小或最佳的替代药物。用于促进骨折愈合的印度草药 Cissus quadrangularis（CQ）已被测试其护骨特性，并研究其有益于骨骼的机制。雌性 Sprague Dawley 大鼠接受假手术或卵巢切除术，并接受 CQ 喂养 3 个月。测定了几种生化标志物、细胞因子和激素。对股骨、胫骨和腰椎进行 pQCT 和 µCT 密度测定。培养 MC3T3 细胞，用 CQ 处理，并用于分析 miRNA 含量，并进行 qPCR 以分析与骨代谢相关的基因表达分析。CQO 大鼠显示出对骨量和远端股骨干骺端和胫骨近端干骺端小梁骨微观结构的保护作用。然而，腰椎没有显示出明显的变化。体内 CQ 治疗后血清 P1NP 蛋白表达水平升高，Trap5b 和 CTX 水平降低。还观察到对抗炎和促炎标志物的一些影响。CQO 大鼠中观察到雌二醇水平显著升高。体外表达的一些与骨代谢相关的基因显示骨钙素显著增加。其他基因-胶原蛋白 I 表达、SPP1、BMP2、DCAT1 表达显著降低。使用 BMP 途径和 Wnt 信号通路调节骨转换的某些 miRNA 被 CQ 上调。CQ 急性处理后的 qPCR 显示骨钙素水平显著升高，Wnt/β catenin 拮抗剂 DCAT1 水平降低。总体而言，CQ 可防止去卵巢引起的长骨微观结构丢失。这可能是因为炎症减少和通过 BMP 和 Wnt 信号通路的调节。我们得出结论，CQ 是一种潜在的治疗绝经后骨质疏松症的药物，没有副作用。
