Paradoxical effects of osteoprotegerin on vascular function: inhibiting inflammation while promoting oxidative stress?

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)379-382
Number of pages4
JournalClinical Science
Volume136
Issue number5
DOIs
StatePublished - Mar 18 2022

Keywords

  • NADPH oxidase
  • RANKL
  • TRAIL
  • osteoprotegerin
  • syndecans

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Paradoxical effects of osteoprotegerin on vascular function: inhibiting inflammation while promoting oxidative stress?'. Together they form a unique fingerprint.

Cite this