Cartilage proteoglycan degradation by a mouse transformed macrophage cell line is mediated by macrophage metalloelastase

M. J. Janusz, M. Hare, S. L. Durham, J. Potempa, W. McGraw, R. Pike, J. Travis, S. D. Shapiro

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Objective and Design: Identify and characterize the matrix metalloproteinase responsible for cartilage proteoglycan degradation mediated by a macrophage cell line in a cell culture model that resembles some aspects of rheumatoid pannus. Materials or Subjects: Supernatants from the transformed mouse macrophage cell line J774A.1 were used to purify the proteoglycan degrading activity. Methods: J774A.1 macrophage culture supernatants were purified by sequential column chromatography and proteins were identified by zymography, western blotting and amino acid sequence analysis. Cartilage degradation was measured using 35S labeled bovine nasal cartilage. Results: The cartilage degrading proteolytic activity in the mouse macrophage supernatants proved to be due to two major proteins with approximate molecular masses of 48 kDa and 22 kDa that were identified as macrophage metalloelastase (MME). Incubation of purified MME at 37°C for up to 16 h resulted in the processing of the 48 kDa protein to several novel bands including a previously undescribed protein of ~ 25 kDa without accumulation of fully processed 22 kDa protein. A number of proteinases increased the rate of this processing. J774A.1 macrophage metalloelastase degraded cartilage proteoglycan with an efficiency approximately equal to human macrophage metalloelastase (MMP-12) and matrilysin (MMP-7) and twice that of stromelysin-1 (MMP-3). Conclusions: These data identify the cartilage proteoglycan degrading metalloproteinase secreted by J774A.1 macrophages in this cell culture model as MME, and describes mechanisms of activation and processing of this enzyme that may play an important role in cartilage degradation.

Original languageEnglish
Pages (from-to)280-288
Number of pages9
JournalInflammation Research
Issue number5
Publication statusPublished - 14 Jun 1999
Externally publishedYes


  • Activation
  • Cartilage degradation
  • Macrophage metalloelastase

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