龟甲提取物通过miR-214调控Wnt/β-catenin信号通路刺激骨形成

LIN Qing; ZHAO Bi-yi; LI Xiao-yun; SUN Wei-peng; HUANG Hong-hao; YANG Yu-mei; WANG Hao-yu; ZHU Xiao-feng; YANG Li; ZHANG Rong-hua

doi:10.1007/s11655-025-4012-9

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龟甲提取物通过miR-214调控Wnt/β-catenin信号通路刺激骨形成

Original Article | Updated：2025-07-30

- 龟甲提取物通过miR-214调控Wnt/β-catenin信号通路刺激骨形成
- Plastrum Testudinis Stimulates Bone Formation through Wnt/β-Catenin Signaling Pathway Regulated by miR-214
- 中国结合医学杂志（英文版） 2025年31卷第8期页码：707-716
- Affiliations：
  
  1.College of Traditional Chinese Medicine, Jinan University, Guangzhou (510632), China
  2.College of Pharmacy, Jinan University, Guangzhou (510632), China
  3.Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Guangzhou (510632), China
- Author bio：
  
  Prof. ZHANG Rong-hua, E-mail: tzrh@jnu.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(U24A6013;82274232;82405121);Guangdong Key Lab of Traditional Chinese Medicine Information Technology(2021B1212040007);Basic and Applied Basic Research Fund of Guangdong Province(2022B1515120022);Construction Project of Guangdong Famous Traditional Chinese Medicine Inheritance Studio of ZHANG Rong-hua(Guangdong Traditional Chinese Medicine Letter (2023) No. 108);China Association for Science and Technology (CAST) Young Talent Support Project Doctoral Student Special Program(CAST Office Letter [2024] No. 92)
- DOI：10.1007/s11655-025-4012-9
  中图分类号：
- 录用日期：2025-02-05，
  
  网络出版日期：2025-05-13，
  
  纸质出版日期：2025-08
- Accepted：
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龟甲提取物通过miR-214调控Wnt/β-catenin信号通路刺激骨形成[J]. 中国结合医学杂志（英文版）, 2025,31(8):707-716.

LIN Qing, ZHAO Bi-yi, LI Xiao-yun, et al. Plastrum Testudinis Stimulates Bone Formation through Wnt/β-Catenin Signaling Pathway Regulated by miR-214[J]. Chinese journal of integrative medicine, 2025, 31(8): 707-716.
龟甲提取物通过miR-214调控Wnt/β-catenin信号通路刺激骨形成[J]. 中国结合医学杂志（英文版）, 2025,31(8):707-716. DOI： 10.1007/s11655-025-4012-9.

LIN Qing, ZHAO Bi-yi, LI Xiao-yun, et al. Plastrum Testudinis Stimulates Bone Formation through Wnt/β-Catenin Signaling Pathway Regulated by miR-214[J]. Chinese journal of integrative medicine, 2025, 31(8): 707-716. DOI： 10.1007/s11655-025-4012-9.

摘要

目的:

探讨龟甲 (Plastrum Testudinis

PT) 提取物在治疗骨质疏松症 (Osteoporosis

OP) 过程中对Wnt信号通路及microRNA (miRNA) 机制的影响.

方法:

将30只雌性Sprague Dawley大鼠通过随机数表法随机分为5组

包括假手术组 (sham group) 、卵巢切除组 (OVX group) 以及高、中、低剂量PT治疗组 (160、80、40 mg/kg/天

每组6只) . 除假手术组外

其余大鼠均行双侧卵巢切除术以模拟骨质疏松症

并连续10周通过口服灌胃给予PT治疗. 治疗后

采用双能X线吸收仪测定骨密度; 通过显微计算机断层扫描和苏木精-伊红染色分析骨微观结构; 并通过免疫组化、Western blot和qRT-PCR检测成骨分化相关因子的表达. 此外

使用Dickkopf-1 (Dkk-1) 抑制骨髓间充质干细胞 (BMSCs) 中的Wnt信号通路

并通过miRNA过表达评估miR-214对BMSCs成骨分化的影响. 随后

利用PT提取物逆转Dkk-1和miR-214的作用

并评估其对BMSCs成骨分化相关因子的影响.

结果:

中、低剂量PT显著降低了OVX大鼠的体重增加 (

0.05) . PT还调节了OVX大鼠股骨的骨量和骨微观结构

与OVX组相比

增加了ALP、BMP-2、COL1A1和RUNX2等成骨相关因子的表达 (

0.05或

0.01) . 同时

不同剂量PT显著逆转了OVX大鼠中Wnt信号通路相关因子的抑制

并增加了Wnt3a、β-catenin、GSK-3β和LRP5的mRNA或蛋白表达 (

0.05或

0.01) . PT刺激了被Dkk-1抑制的BMSCs成骨分化

并激活了Wnt信号通路. 此外

OVX大鼠中miR-214的表达降低 (

0.01)

且与BMSCs的成骨分化呈负相关 (

0.01) . miR-214模拟物抑制了BMSCs中的Wnt信号通路 (

0.05或

0.01) . 相反

PT有效地逆转了miR-214模拟物的作用

从而激活了Wnt信号通路并刺激了BMSCs的成骨分化 (

0.05或

0.01) .

结论:

PT通过β-catenin介导的Wnt信号通路刺激OVX大鼠的骨形成

这可能与抑制BMSCs中的miR-214有关.

Abstract

Objective:

To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of

Plastrum Testudinis

(PT) in the treatment of osteoporo

sis (OP).

Methods:

Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method

including sham group

ovariectomized group (OVX)

ovariectomized groups treated with high-

medium-

and low-dose PT (160

40 mg/kg per day

respectively)

with 6 rats in each group. Except for the sham group

the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment

bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry

Western blot

and quantitative polymerase chain reaction. In addition

Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently

PT extract was used to rescue the effects of Dkk-1 and miR-214

and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated.

Results:

PT-M and PT-L significantly reduced the weight gain in OVX rats (

0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats

and increased the expressions of bone formation-related factors including alkaline phosphatase

bone morphogenetic protein type 2

collagen type Ⅰ alpha 1

and runt-related transcription factor 2 when compared with the OVX group (

0.05 or

0.01). Meanwhile

different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats

and increased the mRNA or protein expressions of Wnt3a

β-catenin

glycogen synthase kinase-3β

and low-density lipoprotein receptor-related protein 5 (

0.05 or

0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition

the expression of miR-214 was decreased in OVX rats (

0.01)

and it was negatively correlated with the osteogenic differentiation of BMSCs (

0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (

0.05 or

0.01). Conversely

PT effectively counteracted the effect of miR-214 mimic

thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (

0.05 or

0.01).

Conclusion:

PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway

which may be related to inhibiting miR-214 in BMSCs.

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