骨密宝汤调节大鼠糖皮质激素性骨质疏松症中骨代谢相关mRNA的表达。

Gumi Bao decoction regulates bone metabolism-related mRNA expression in glucocorticoid-induced osteoporosis in rats.

作者信息

Feng Huanhuan, Gong Zhengfeng, Liang Guoqiang, Shen Xiaofeng, Cheng Jian, Su Fangdong, Yang Lizhong, Liu Hua

机构信息

Department of First Clinical Medical Institute, Nanjing University of Chinese Medicine, Nanjing, China; Department of Orthopedics, Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Taicang, China.

Department of Orthopedics, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.

出版信息

Ann Palliat Med. 2020 Sep;9(5):3213-3221. doi: 10.21037/apm-20-1340.

DOI:10.21037/apm-20-1340

PMID:33065783

Abstract

BACKGROUND

Gumi Bao decoction is effective for the treatment of osteoporosis, but the theoretical and scientific basis is unknown. This study aimed to observe the effect of Gumi Bao decoction on Dickkopf-related protein 1 (DKK1) mRNA, runt-related transcription factor 2 (Runx2) mRNA, and cathepsin K (CTSK) mRNA in glucocorticoid-induced osteoporosis (GIOP) in rats and to investigate the underlying mechanism.

METHODS

Sixty Sprague-Dawley (SD) rats were weighed and randomly divided into six groups: the normal control group (NC group), the methylprednisolone group (Met group), the Fosamax group, the low-dose Gumi Bao Decoction group (GBDL group), the medium-dose Gumi Bao Decoction group (GBDM group), and the high-dose Gumi Bao Decoction group (GBDH group). The basic physiological conditions of the rats and the bone morphology of the fourth lumbar vertebra and the left femur of three rats in each group were observed, and the mRNA expressions of bone tissue-related genes were detected.

RESULTS

After administration, DKK1 mRNA expression was significantly up-regulated in the Met group compared to the NC group (P<0.001). Meanwhile, DKK1 mRNA was significantly down-regulated in the Fosamax group compared with the Met group (P<0.001). There was a significant difference in the down-regulation of DKK1 mRNA between the GBDM and GBDH groups (P<0.001). Runx2 mRNA was considerably down-regulated in the Met group compared with the NC group (P<0.001). Runx2 mRNA was up-regulated in the GBDM group, and the GBDH group was significantly different compared to the Met group (P<0.001). CTSK mRNA was significantly up-regulated in the Met group compared to the NC group (P<0.001). Compared with the Met group, CTSK mRNA expression was significantly down-regulated in the Fosamax group (P<0.001), as well as in the GBDL, GBDM, and GBDH groups (P<0.001). At 200× and 400×, there were significantly fewer osteoblasts and osteoclasts in the Met group than in the Fosamax, GBDM, and GBDH groups.

CONCLUSIONS

The imbalance of bone homeostasis of GIOP is caused by an increase in bone resorption and decreased osteogenesis. Gumi Bao could regulate bone metabolism through the action of DKK1 via the Wnt/β-catenin signaling pathway, up-regulating Runx2 mRNA and down-regulating CTSK mRNA.

摘要

背景

骨密宝汤剂对骨质疏松症具有治疗作用，但其理论及科学依据尚不清楚。本研究旨在观察骨密宝汤剂对糖皮质激素诱导的骨质疏松症（GIOP）大鼠中 Dickkopf 相关蛋白 1（DKK1）mRNA、 runt 相关转录因子 2（Runx2）mRNA 和组织蛋白酶 K（CTSK）mRNA 的影响，并探讨其潜在机制。

方法

将 60 只 Sprague-Dawley（SD）大鼠称重后随机分为 6 组：正常对照组（NC 组）、甲泼尼龙组（Met 组）、福善美组、低剂量骨密宝汤剂组（GBDL 组）、中剂量骨密宝汤剂组（GBDM 组）和高剂量骨密宝汤剂组（GBDH 组）。观察大鼠的基本生理状况以及每组 3 只大鼠第四腰椎和左股骨的骨形态，并检测骨组织相关基因的 mRNA 表达。

结果

给药后，与 NC 组相比，Met 组 DKK1 mRNA 表达显著上调（P<0.001）。同时，与 Met 组相比，福善美组 DKK1 mRNA 显著下调（P<0.001）。GBDM 组和 GBDH 组在 DKK1 mRNA 下调方面存在显著差异（P<0.001）。与 NC 组相比，Met 组 Runx2 mRNA 显著下调（P<0.001）。GBDM 组 Runx2 mRNA 上调，且 GBDH 组与 Met 组相比有显著差异（P<0.001）。与 NC 组相比，Met 组 CTSK mRNA 显著上调（P<0.001）。与 Met 组相比，福善美组以及 GBDL、GBDM 和 GBDH 组 CTSK mRNA 表达均显著下调（P<0.001）。在 200 倍和 400 倍视野下，Met 组的成骨细胞和破骨细胞明显少于福善美组、GBDM 组和 GBDH 组。