Matrix proteins with high affinity for calcium ions are associated with mineralization within the elastic fibers of pseudoxanthoma elasticum dermis

• Published in: The American journal of pathology Vol. 148; no. 2; pp. 569 - 577
• Main Authors: Contri, MB, Boraldi, F, Taparelli, F, De Paepe, A, Ronchetti, IP
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.02.1996; American Society for Investigative Pathology
• Subjects: Adolescent; Adult; Alkaline Phosphatase - analysis; Biological and medical sciences; Calcinosis; Calcium - metabolism; Dermatology; Elastic Tissue - chemistry; Elastic Tissue - pathology; Extracellular Matrix Proteins - analysis; Extracellular Matrix Proteins - metabolism; Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue; Humans; Integrin-Binding Sialoprotein; Medical sciences; Microscopy, Electron; Microscopy, Immunoelectron; Osteonectin - analysis; Osteopontin; Pseudoxanthoma Elasticum - metabolism; Pseudoxanthoma Elasticum - pathology; Sialoglycoproteins - analysis; Skin - metabolism; Skin - pathology; Skin - ultrastructure; Vitronectin - analysis; Human; Immunohistochemistry; Skin disease; Immunogold labelling; Elastic tissue disease; Pathogenesis; Vitronectin; Electron microscopy; Fibronectin; Genetic disease; Proteins; Pathology; Calcium ion; Affinity; Extracellular matrix; Pseudoxanthoma elasticum
• ISSN: 0002-9440; 1525-2191

Ultrathin sections from the dermis of five normal subjects and from 10 patients suffering from pseudoxanthoma elasticum (PXE) were analyzed by immunoelectron microscopy with the aim of identifying and localizing proteins associated with the mineral precipitates within the altered elastic fibers. Serial sections were processed by indirect immunogold cytochemistry using primary antibodies against human fibronectin, vitronectin, bone sialoprotein, alkaline phosphatase, osteonectin, and osteopontin. In the latter two cases, antibodies against synthetic peptides were also used. The results indicate that normal elastic fibers contained osteopontin, and that this protein was associated with the apparently normal elastin as well as with the needle-shaped mineral precipitates in the elastic fibers of patients. On the contrary, significant amounts of vitronectin, alkaline phosphatase and, less, of bone sialoprotein were associated with the polymorphous mineral precipitates inside the elastic fibers. Large amounts of osteonectin and fibronectin, together with vitronectin, were localized on the microfilament aggregates, which were often associated with altered elastic fibers in PXE dermis and were never visualized in the dermis of control subjects. The results seem to indicate once more that PXE is a complex disorder of the fibroblast synthetic control. Elastic fiber mineralization might be considered a secondary event, which could depend on the abnormal synthesis and accumulation within the elastic fibers of proteins that are normally involved in mineralization processes.