Annexin-mediated matrix vesicle calcification in vascular smooth muscle cells

Neal X. Chen, Kalisha D. O'Neill, Xianming Chen, Sharon M. Moe

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

In bone, osteoblasts and chondrocytes synthesize matrix vesicles (MVs) that interact with collagen to initiate calcification. MVs have been identified in human calcified arteries but are poorly characterized. The objective of this study is to determine the role of annexins and fetuin-A in MV formation and activity during calcification in bovine vascular smooth muscle cells (BVSMCs). BVSMCs were treated with control or calcification (high phosphorus) media, and cellular MVs were isolated by collagenase digestion and secreted MVs were isolated from cultured media by ultracentrifugation. The results showed that alkaline phosphatase (ALP) activity was significantly increased in MVs from calcified BVSMCs compared with non-calcified BVSMCs, as was annexin II and VI content and 45Ca uptake. We also determined that MVs from calcifying BVSMCs could mineralize type I collagen but not type II collagen in the absence of cells in a dose-and time-dependent manner. Blockade of annexin calcium channel activity by K201 significantly decreased ALP activity and reduced the ability of the MVs to subsequently calcify on collagen, whether the K201 was added during or after MV formation. Furthermore, cellular MVs had significantly increased ability to calcify on collagen compared with secreted MVs, likely because of their increased ALP activity and annexin II content but low fetuin-A content. In conclusion, our results suggest that mineralization in VSMCs requires both active MVs and an interaction of the MVs with type I collagen, and both steps require annexin activity.

Original languageEnglish (US)
Pages (from-to)1798-1805
Number of pages8
JournalJournal of Bone and Mineral Research
Volume23
Issue number11
DOIs
StatePublished - Nov 1 2008

Keywords

  • Annexins
  • Calcification
  • Fetuin-A
  • Matrix vesicles
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

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