Human vascular cell responses to the circulating bone hormone osteocalcin.

Area of Science:

• Vascular Biology
• Endocrinology
• Cell Signaling

Background:

• Osteocalcin is a bone-derived hormone with known systemic effects.
• Uncarboxylated osteocalcin (ucOCN) is the active form influencing various cellular processes.
• The direct impact of ucOCN on vascular cells and its role in atherosclerosis remain incompletely understood.

Purpose of the Study:

• To investigate the direct effects of ucOCN on human aortic endothelial cells (HAECs) and smooth muscle cells (HASMCs) in vitro.
• To determine ucOCN's potential role in the pathophysiology of atherosclerosis.

Main Methods:

• HAECs and HASMCs were treated with varying concentrations of ucOCN.
• Key cellular responses including protein phosphorylation, proliferation, angiogenesis, migration, permeability, and protein secretion were assessed.
• Specific signaling pathways (JNK, CREB, p70S6K, NF-κB, AKT, ERK) were analyzed.

Main Results:

• ucOCN modulated intracellular signaling pathways in both cell types, decreasing p-JNK and p-CREB in HAECs while increasing p-p70S6K and p-NF-κB in HASMCs.
• Dose-dependent increases in cell proliferation were observed in both HAECs and HASMCs, inhibited by AKT and ERK pathway blockers.
• ucOCN did not significantly alter cell permeability, angiogenesis, or migration.

Conclusions:

• Uncarboxylated osteocalcin directly influences vascular cell biology, notably promoting proliferation.
• Despite observed signaling changes, ucOCN does not appear to directly promote atherogenesis in vitro under the conditions tested.