In:
Chinese Medicine, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2023-08-29)
Abstract:
Angiogenesis is regarded as a critical role in bone repair and regeneration, involving in pathological bone disorders such as osteoporosis. Aucubin, an iridoid glycoside primarily derived from Eucommia ulmoides , is reported to inhibit osteoclast activity, enhance bone formation and promote angiogenesis in osteoporosis models. Our study is to further investigate the anti-osteoporosis effect of aucubin in transgenic medaka, and the pro-angiogenic effect of aucubin and its mechanism of action both in vivo and in vitro. Methods The anti-osteoporosis effect of aucubin was confirmed by using RANKL-stimulated bone resorption transgenic medaka. The pro-angiogenic effect of aucubin in vivo was investigated using vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor II (VRI)-induced vascular insufficient transgenic zebrafish model. Furthermore, endothelial cell proliferation, migration, tube formation and the mechanisms were evaluated to identify the pro-angiogenic effect of aucubin in normal and su5416-injured human umbilical vein endothelial cells (HUVECs). Results Aucubin decreased the resorption of the mineralized bone matrix and centra degradation in heat-shocked transgenic col10α1:nlGFP/rankl:HSE:CFP medaka. Moreover, aucubin reversed VRI-induced vascular insufficiency in zebrafish through regulating flt1 , kdr , kdrl , vegfaa , ang-1 , ang-2 , tie1 and tie2 mRNA expressions in Tg(fli1a:EGFP) y1 or AB wild type zebrafish. Aucubin promoted cell proliferation by upregulating p-mTOR, p-Src, p-MEK, p-Erk1/2, p-Akt and p-FAK in HUVECs. Furthermore, aucubin exhibited a pro-angiogenic effect on su5416-injured HUVECs by promoting their proliferation, migration, and tube formation through regulating the phosphorylation of VEGFR2, MEK, ERK and the ratio of Bcl2-Bax. Conclusion Aucubin could reduce bone resorption in RANKL-induced osteoporosis medaka by live imaging. Meanwhile, aucubin exhibited a protective effect in VRI-induced vascular insufficient zebrafish by regulating VEGF-VEGFR and Ang-Tie signaling pathways. Additionally, aucubin promoted the proliferation, migration and tube formation of HUVECs probably by mediating VEGFR2/MEK/ERK, Akt/mTOR and Src/FAK signalling pathways. This study further indicated the dual effect of aucubin on angiogenesis and osteogenesis which may be beneficial to its treatment of osteoporosis.
Type of Medium:
Online Resource
ISSN:
1749-8546
DOI:
10.1186/s13020-023-00786-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2260322-0
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