Salidroside improves angiogenesis-osteogenesis coupling by regulating the HIF-1α/VEGF signalling pathway in the bone...

Area of Science:

• Biomedical Science
• Molecular Biology
• Regenerative Medicine

Background:

• Angiogenesis and osteogenesis are crucial for skeletal development and bone repair.
• The hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) pathway are key regulators coupling angiogenesis and osteogenesis.
• Salidroside (SAL), a compound from Rhodiola rosea L., has various pharmacological effects, but its role in bone healing via angiogenesis-osteogenesis coupling was unclear.

Purpose of the Study:

• To investigate the effects of Salidroside (SAL) on endothelial cells and the HIF-1α/VEGF signaling pathway.
• To determine if SAL can induce angiogenesis-osteogenesis coupling in vitro and in vivo.
• To explore SAL as a potential therapeutic agent for accelerating bone healing.

Main Methods:

• In vitro studies using primary human umbilical vein endothelial cells (HUVECs) and EA.hy926 cells treated with SAL or conditioned medium from SAL-treated osteoblasts (MG-63 cells).
• Assessment of endothelial cell proliferation, migration, and capillary structure formation.
• In vivo analysis of SAL's effect on endothelial sprouting from metatarsal bones.
• Investigation of HIF-1α expression, transcriptional activity, and VEGF levels (mRNA and protein).

Main Results:

• SAL treatment enhanced endothelial cell proliferation, migration, and capillary-like structure formation in vitro.
• The pro-angiogenic effects of SAL were reversed by an anti-VEGF antibody, indicating VEGF dependency.
• SAL upregulated HIF-1α expression and transcriptional activity, leading to increased VEGF expression.
• In vivo studies showed SAL stimulates endothelial sprouting from bone, confirming its pro-angiogenic role in the bone environment.

Conclusions:

• Salidroside (SAL) promotes angiogenesis and osteogenesis coupling through the HIF-1α/VEGF signaling pathway.
• SAL demonstrates potential as a therapeutic agent for accelerating bone healing by enhancing both blood vessel formation and bone formation.
• This study elucidates a novel mechanism for SAL in bone repair, highlighting its dual pro-angiogenic and osteogenic properties.