Peroxidase Enzymes Regulate Collagen Biosynthesis and Matrix Mineralization by Cultured Human Osteoblasts

Mark O. DeNichilo, Alexandra J. Shoubridge, Vasilios (Bill) Panagopoulos, Vasilios Liapis, Aneta Zysk, Irene Zinonos, Shelley Hay, Gerald J. Atkins, David M. Findlay, Andreas Evdokiou

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The early recruitment of inflammatory cells to sites of bone fracture and trauma is a critical determinant in successful fracture healing. Released by infiltrating inflammatory cells, myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are heme-containing enzymes, whose functional involvement in bone repair has mainly been studied in the context of providing a mechanism for oxidative defense against invading microorganisms. We report here novel findings that show peroxidase enzymes have the capacity to stimulate osteoblastic cells to secrete collagen I protein and generate a mineralized extracellular matrix in vitro. Mechanistic studies conducted using cultured osteoblasts show that peroxidase enzymes stimulate collagen biosynthesis at a post-translational level in a prolyl hydroxylase-dependent manner, which does not require ascorbic acid. Our studies demonstrate that osteoblasts rapidly bind and internalize both MPO and EPO, and the catalytic activity of these peroxidase enzymes is essential to support collagen I biosynthesis and subsequent release of collagen by osteoblasts. We show that EPO is capable of regulating osteogenic gene expression and matrix mineralization in culture, suggesting that peroxidase enzymes may play an important role not only in normal bone repair, but also in the progression of pathological states where infiltrating inflammatory cells are known to deposit peroxidases.

Original languageEnglish
Pages (from-to)294-305
Number of pages12
JournalCalcified Tissue International
Volume98
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016

Keywords

  • Collagen biosynthesis
  • Matrix mineralization
  • Osteoblasts
  • Peroxidase enzymes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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