The fate of cartilage oligomeric matrix protein is determined by the cell type in the case of a novel mutation in pseudoachondroplasia

B. Kerry Maddox, Douglas R. Keene, Lynn Y. Sakai, Noé L. Charbonneau, Nicholas P. Morris, Catherine C. Ridgway, Bruce A. Boswell, Michael D. Sussman, William A. Horton, Hans Peter Bächinger, Jacqueline T. Hecht

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Abstract

We have identified a novel missense mutation in a pseudoachondroplasia (PSACH) patient in one of the type III repeats of cartilage oligomeric matrix protein (COMP). Enlarged lamellar rough endoplasmic reticulum vesicles were shown to contain accumulated COMP along with type IX collagen, a cartilage- specific component. COMP was secreted and assembled normally into the extracellular matrix of tendon, demonstrating that the accumulation of COMP in chondrocytes was a cell-specific phenomenon. We believe that the intracellular storage of COMP causes a nonspecific aggregation of cartilage- specific molecules and results in a cartilage matrix deficient in required structural components leading to impaired cartilage growth and maintenance. These data support a common pathogenetic mechanism behind two clinically related chondrodysplasias, PSACH and multiple epiphyseal dysplasia.

Original languageEnglish (US)
Pages (from-to)30993-30997
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number49
DOIs
StatePublished - Dec 5 1997

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Maddox, B. K., Keene, D. R., Sakai, L. Y., Charbonneau, N. L., Morris, N. P., Ridgway, C. C., Boswell, B. A., Sussman, M. D., Horton, W. A., Bächinger, H. P., & Hecht, J. T. (1997). The fate of cartilage oligomeric matrix protein is determined by the cell type in the case of a novel mutation in pseudoachondroplasia. Journal of Biological Chemistry, 272(49), 30993-30997. https://doi.org/10.1074/jbc.272.49.30993