Biosynthesis of the vitamin K-dependent matrix Gla protein (MGP) in chondrocytes: a fetuin-MGP protein complex is assembled in vesicles shed from normal but not from osteoarthritic chondrocytes

R. Wallin, L. J. Schurgers, R. F. Loeser*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Web of Science)

Abstract

Objective: Mineralization has been observed in osteoarthritic cartilage but the mechanisms are incompletely understood. Vitamin K is an essential cofactor in post-translational modification of proteins where specific Glu residues become modified to Ca++ binding gamma-carboxyglutamic acid residues (Gla). One such protein, matrix Gla protein (MGP), is a known mineralization inhibitor. This study determined if synthesis of MGP and formation of a fetuin-MGP protein complex was altered in chondrocytes and vesicles from osteoarthritis (OA) cartilage. Methods: Chondrocytes and vesicles were isolated from normal and OA human articular cartilage and lysates prepared. Specific antibodies were used in immunoblotting to detect the mature fully gamma-carboxylated form of MGP (cMGP) and non-gamma-carboxylated MGP (ucMGP) as well as fetuin and MGP fetuin complexes. gamma-carboxylase activity was measured by (CO2)-C-14 incorporation into the carboxylase peptide substrate FLEEL. Immunocytochemistry was used to examine fetuin in cartilage sections and uptake of biotin-labeled fetuin by isolated chondrocytes. Results: Chondrocytes and vesicles from osteoarthritic tissue produced significantly less cMGP compared to those from normal cartilage. This correlated with significantly less vitamin K-dependent gamma-carboxylase enzyme activity in OA chondrocytes. Fetuin was found to be present in articular cartilage and cultured chondrocytes were capable of fetuin uptake. A fetuin-MGP complex was identified in normal chondrocytes and in vesicles shed from these cells but not in OA cells or vesicles. Conclusions: The absence of cMGP and of the cMGP-fetuin complex in OA cells and OA vesicles may be an important mechanism for increased mineralization of osteoarthritic cartilage.
Original languageEnglish
Pages (from-to)1096-1103
JournalOsteoarthritis and Cartilage
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Vitamin K
  • Articular cartilage
  • Osteoarthritis
  • Matrix Gla protein
  • Fetuin

Cite this