Calcified Tissue International

, Volume 59, Issue 2, pp 109–116 | Cite as

Vitamin D Metabolites Regulate Matrix Vesicle Metalloproteinase Content in a Cell Maturation-Dependent Manner

  • D. D. Dean
  • B. D. Boyan
  • O. E. Muniz
  • D. S. Howell
  • Z. Schwartz
Laboratory Investigations


Matrix vesicles are extracellular organelles produced by cells that mineralize their matrix. They contain enzymes that are associated with calcification and are regulated by vitamin D metabolites in a cell maturation-dependent manner. Matrix vesicles also contain metalloproteinases that degrade proteoglycans, macromolecules known to inhibit calcificationin vitro, as well as plasminogen activator, a proteinase postulated to play a role in activation of latent TGF-\. In the present study, we examined whether matrix vesicle metalloproteinase and plasminogen activator are regulated by 1,25(OH)2D3 and 24,25 (OH)2D3. Matrix vesicles and plasma membranes were isolated from fourth passage cultures of resting zone chondrocytes that had been incubated with 1010-10-7 M24,25(OH)2D3 or growth zone chondrocytes incubated with 10-11-l0-8 M 1,25(OH)2D3, and their alkaline phosphatase, active and total neutral metalloproteinase, and plasminogen activator activities determined. 24,25(OH)2D3 increased alkaline phosphatase by 35–60%, decreased active and total metalloproteinase by 75%, and increased plasminogen activator by fivefold in matrix vesicles from resting zone chondrocyte cultures. No effect of vitamin D treatment was observed in plasma membranes isolated from these cultures. In contrast, 1,25(OH)2D3 increased alkaline phosphatase by 35–60%, but increased active and total metalloproteinase three- to fivefold and decreased plasminogen activator by as much as 75% in matrix vesicles isolated from growth zone chondrocyte cultures. Vitamin D treatment had no effect on plasma membrane alkaline phosphatase or metalloproteinase, but decreased plasminogen activator activity. The results demonstrate that neutral metalloproteinase and plasminogen activator activity in matrix vesicles are regulated by vitamin D metabolites in a cell maturation-specific manner. In addition, they support the hypothesis that 1,25(OH)2D3 regulation of matrix vesicle function facilitates calcification by increasing alkaline phosphatase and phospholipase A2 specific activities as well as metalloprotemases which degrade proteoglycans.

Key words

Metalloproteinases Matrix vesicles Chondrocytes Calcification 1,25(OH)2D3 24,25(OH)2D3 


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Copyright information

© Springer-Verlag New York Inc. 1996

Authors and Affiliations

  • D. D. Dean
    • 1
  • B. D. Boyan
    • 1
    • 2
    • 3
  • O. E. Muniz
    • 4
  • D. S. Howell
    • 4
  • Z. Schwartz
    • 1
    • 2
    • 5
  1. 1.Department of OrthopaedicsUniversity of Texas Health Texas Science Center at San AntonioSan Antonio
  2. 2.Department of PeriodonticsUniversity of Texas Health Science Center at San AntonioSan Antonio
  3. 3.Department of BiochemistryUniversity of Texas Health Science Center at San AntonioSan Antonio
  4. 4.Miami Department of Veterans Affairs Medical Center, and Department of MedicineThe University of Miami School of MedicineMiamiUSA
  5. 5.Department of PeriodonticsHebrew University Hadassah Faculty of Dental MedicineJerusalemIsrael

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