Paradoxical Effects of Osteoprotegerin on Vascular Function: Inhibiting Inflammation While Promoting Oxidative Stress?

Authors

Nhat-Tu Le
Elizabeth A Olmsted-Davis
Jun-Ichi Abe

Publication Date

3-18-2022

Journal

Clinical Science

DOI

10.1042/CS20211096

PMID

35274135

PMCID

PMC8919090

PubMedCentral® Posted Date

3-11-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor or tumor necrosis factor receptor superfamily member 11B, is well known as a modulator of bone remodeling. The contribution of OPG to cardiovascular disease (CVD) has been suggested, but its molecular mechanism is complex and remains unclear. In the present study, Alves-Lopes et al. (Clin. Sci. (Lond.) (2021) 135(20): https://doi.org/10.1042/CS20210643) reported the critical role of syndecan-1 (SDC-1, also known as CD138), a surface protein part of the endothelial glycocalyx, in OPG-induced vascular dysfunction. The authors found that in endothelial cells (ECs), through SDC-1, OPG increased eNOS Thr495 phosphorylation, thereby inhibiting eNOS activity. Furthermore, the OPG-SDC-1 interaction increased reactive oxygen species (ROS) production through NOX1/4 activation. Both the reduced eNOS activity and induced ROS production inhibited NO production and impaired EC function. In vascular smooth muscle cells (VSMCs), the OPG-SDC-1 interaction increased ROS production through NOX1/4 activation, subsequently increased MLC phosphorylation-mediated Rho kinase-MYPT1 regulation, leading to increased vascular contraction. Ultilizing wire myography and mechanistic studies, the authors nicely provide the evidence that SDC-1 plays a crucial role in OPG-induced vascular dysfunction. As we mentioned above, the molecular mechanism and roles of OPG in cardiovascular system are complex and somewhat confusing. In this commentary, we briefly summarize the OPG-mediated signaling pathways in cardiovascular system.

Keywords

Endothelial Cells, Humans, Inflammation, Osteoprotegerin, Oxidative Stress, Reactive Oxygen Species, NADPH oxidase, osteoprotegerin, RANKL, syndecans, TRAIL

Published Open-Access

yes

Recommended Citation

Nhat-Tu Le, Elizabeth A Olmsted-Davis, and Jun-Ichi Abe, "Paradoxical Effects of Osteoprotegerin on Vascular Function: Inhibiting Inflammation While Promoting Oxidative Stress?" (2022). Faculty, Staff and Student Publications. 2438.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/2438