Up-regulated expression of the phosphodiesterase nucleotide pyrophosphatase family member PC-1 is a marker and pathogenic factor for knee meniscal cartilage matrix calcification

Arthritis Rheum. 2001 May;44(5):1071-81. doi: 10.1002/1529-0131(200105)44:5<1071::AID-ANR187>3.0.CO;2-3.


Objective: Elevated cartilage inorganic pyrophosphate (PPi) production and PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity are strongly linked with aging-related cartilage calcification in meniscal and articular cartilages. We hypothesized that there were divergent relationships of 3 NTPPPH isozymes with cartilage matrix calcification and sought to identify them.

Methods: We studied knee medial meniscal expression in situ of 3 NTPPPH isozymes of the phosphodiesterase nucleotide pyrophosphatase (PDNP) family: plasma cell membrane glycoprotein 1 (PC-1, or PDNP1), autotaxin (ATX, or PDNP2), and B10/PDNP3. We also used complementary DNA transfection to assess differential functions in matrix calcification of each NTPPPH isozyme in vitro in meniscal cells.

Results: We observed diffuse cell-associated ATX and B10/PDNP3 expression in central (chondrocytic) and, to a lesser degree, peripheral (fibroblastic) regions of normal, degenerative uncalcified, and degenerative calcified menisci. In contrast, PC-1 expression was only robust at sites of apoptotic cells and calcification in central regions of degenerative menisci. Only PC-1 was abundant at the perimeter of meniscal cells and in association with meniscal cell-derived matrix vesicles (MVs). Because each PDNP-family isozyme was expressed by cells near calcifications, we transfected the isozymes in nonadherent knee meniscal cells cultured with ascorbic acid, beta-glycerophosphate, and dexamethasone supplementation to stimulate them to calcify the matrix. PC-1, but not ATX or B10/PDNP3, consistently promoted increased MV NTPPPH, MV-associated PPi, and extracellular PPi. PC-1 also increased matrix calcification (with hydroxyapatite crystals) by meniscal cells. ATX uniquely induced alkaline phosphatase activity, but promoted only moderately increased matrix calcification.

Conclusion: We identified divergent effects of 3 PDNP-family NTPPPH isozymes on meniscal cell matrix calcification. Increased expression of PC-1 is both a marker and a potential pathogenic factor for knee meniscal cartilage matrix calcification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / pathology
  • Biomarkers
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Cartilage, Articular / cytology
  • Cartilage, Articular / enzymology
  • Cartilage, Articular / pathology
  • Cells, Cultured
  • Chondrocalcinosis / metabolism*
  • Chondrocalcinosis / pathology*
  • Extracellular Matrix / enzymology
  • Extracellular Matrix / pathology
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Enzymologic
  • Glucose-6-Phosphate Isomerase / metabolism
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Knee Joint / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Multienzyme Complexes*
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / pathology*
  • Phosphates / metabolism
  • Phosphodiesterase I
  • Phosphoric Diester Hydrolases*
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism
  • Transfection


  • Biomarkers
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Isoenzymes
  • Membrane Glycoproteins
  • Multienzyme Complexes
  • Phosphates
  • Phosphoric Diester Hydrolases
  • Enpp3 protein, rat
  • Phosphodiesterase I
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • alkylglycerophosphoethanolamine phosphodiesterase
  • CILP protein, human
  • Pyrophosphatases
  • nucleoside triphosphate pyrophosphatase
  • Glucose-6-Phosphate Isomerase