Total flavonoids of Rhizoma Drynariae enhances CD31hiEmcnhi vessel formation and subsequent bone regeneration in rat models of distraction osteogenesis by activating PDGF-BB/VEGF/RUNX2/OSX signaling axis

被引：9

作者：

Shen, Zhen ^{[1
]}

Dong, Wei ^{[1
]}

Chen, Zehua ^{[1
]}

Chen, Guoqian ^{[2
]}

Zhang, Yan ^{[3
]}

Li, Zige ^{[3
]}

Lin, Haixiong ^{[3
]}

Chen, Huamei ^{[3
]}

Huang, Minling ^{[3
]}

Guo, Ying ^{[1
]}

Jiang, Ziwei ^{[4
]}

机构：

[1] Yunnan Univ Chinese Med, Kunming Municipal Hosp Tradit Chinese Med, Affiliated Hosp 3, Dept Orthopaed, Kunming 650599, Yunnan, Peoples R China

[2] Guangzhou Univ Chinese Med, Clin Med Coll 5, Guangzhou 510405, Guangdong, Peoples R China

[3] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou 510407, Guangdong, Peoples R China

[4] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Orthopaed, Guangzhou 510407, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2022年 / 50卷 / 03期

基金：

中国国家自然科学基金;

关键词：

total flavonoids of Rhizoma Drynariae; CD31(hi)Emcn(hi) vessels; distraction osteogenesis; platelet-derived growth factor-BB; bone regeneration; ANGIOGENESIS; CELLS; PROMOTES; GROWTH; REPAIR; PDGF;

D O I：

10.3892/ijmm.2022.5167

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney-tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31(hi)Emcn(hi) during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31(hi)Emcn(hi) vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co-immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31(hi)Emcn(hi) vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet-derived growth factor (PDGF)-BB, VEGF, runt-related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription-quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31(hi)Emcn(hi) vessel formation during DO, whereas PDGF-BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF-BB. The protein and mRNA levels of PDGF-BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF-BB. Thus, TFRD could facilitate CD31(hi)Emcn(hi) vessel formation and subsequently enhance angiogenic-osteogenic coupling to regenerate bone defects during DO via the PDGF-BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31(hi)Emcn(hi) vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31(hi)Emcn(hi) vessels.

引用

页数：13

共 1 条

[1] Total Flavonoids of Rhizoma Drynariae Enhances Angiogenic-Osteogenic Coupling During Distraction Osteogenesis by Promoting Type H Vessel Formation Through PDGF-BB/PDGFR-β Instead of HIF-1α/ VEGF Axis
Shen, Zhen
Chen, Zehua
Li, Zige
Zhang, Yan
Jiang, Tao
Lin, Haixiong
Huang, Minling
Chen, Huamei
Feng, Junjie
Jiang, Ziwei
FRONTIERS IN PHARMACOLOGY, 2020, 11

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