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

Osteoarthritis Cartilage. 2010 Aug;18(8):1096-103. doi: 10.1016/j.joca.2010.05.013. Epub 2010 May 25.


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 (14)CO(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / biosynthesis*
  • Cartilage, Articular / metabolism*
  • Chondrocytes / metabolism*
  • Extracellular Matrix Proteins / biosynthesis*
  • Humans
  • Osteoarthritis / metabolism*
  • Protein Processing, Post-Translational
  • Vitamin K / biosynthesis*
  • alpha-Fetoproteins / metabolism*


  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • alpha-Fetoproteins
  • matrix Gla protein
  • Vitamin K