ATP-Dependent Mineralization of Hyaline Articular Cartilage Matrix Vesicles

Abstract

Cartilage matrix vesicles are particulate structures found in the extracellular matrix of epiphyseal and articular cartilage (1). These membrane-bound particles of membranes contain enzyme activities including ATP pyrophosphohydrolase and 51 nucleotidase (Figure 1). Mineralization of matrix vesicles is believed to play an important role in cartilage calcification (1, 2). In some in vitro systems, the mineralization of matrix vesicles is an ATP-dependent process (3, 4). Adenosine deaminase (ADA) deficiency, an inborn error of metabolism that causes severe combined immunodeficiency disease, is associated with chondro-osseous dysplasia (5, 6). The chondro-osseous dysplasia is associated with radiographic and histologic evidence of abnormal calcification of growth plate cartilage (7, 8). The cause of the abnormal calcification is unknown. In vitro, a model of ADA deficiency is toxic to growth plate cartilage. The toxicity is associated with accumulatuion of deoxyATP but correlates with ATP depletion in chondrocytes (9). Studies were performed to understand the biochemistry of matrix vesicle mineralization and to test the hypothesis that the abnormal calcification observed in the chondro-osseous dysplasia of ADA deficiency is caused by abnormal matrix vesicle mineralization secondary to ATP depletion.