ABSTRACT
OBJECTIVE: To assess the expression of calpains and calpain-induced aggrecan fragmentation in early and advanced stages of degeneration of human intervertebral discs (IVDs). DESIGN: Disc tissue samples of 55 patients (mean age, 51.2 ± 22.3 years) who underwent intervertebral fusion were divided into groups with early and advanced degeneration based on the Thompson magnetic resonance imaging (MRI) scale. In advanced degeneration group, five patients (mean age, 35.5 ± 11.4 years) of lumbar disc herniation (LDH) were included. Protein levels of m- and µ-calpains and their inhibitor calpastatin were assayed, and immunohistochemical techniques were used to localize and quantify the production of the enzymes. To investigate calpain activity, we assayed purified aggrecan fragmentation in disc tissue by Western blotting and immunohistochemistry with VPGVA antibody, which recognizes the m-calpain generated neo-epitope GVA. RESULTS: Discs at early stages of degeneration expressed low levels of m- and µ-calpains and calpastatin, and few cells expressed degenerative enzymes. At more advanced stages of degeneration, the expression and number of cells immunopositive for m-calpain, µ-calpain and calpastatin were significantly higher. Further finding showed that anti-GVA-reactive aggrecan fragments were significantly higher in discs at advanced compared with early stages of degeneration. Herniated disc samples showed stronger expression and more cells immunopositive for calpains, calpastatin and GVA in the nucleus pulposus than in the annulus fibrous. CONCLUSIONS: The expression of calpains, together with m-calpain-induced degradation products of extracellular matrix, was correlated with the degree of disc degeneration in human IVD tissue. These findings suggest that calpains may be involved in IVD degeneration via proteoglycan (PG) cleavage.
Subject(s)
Aggrecans/metabolism , Calcium-Binding Proteins/physiology , Calpain/metabolism , Intervertebral Disc Degeneration/metabolism , Lumbar Vertebrae/enzymology , Adolescent , Adult , Aged , Aged, 80 and over , Blotting, Western , Calpain/antagonists & inhibitors , Child , Extracellular Matrix/pathology , Extracellular Matrix Proteins/metabolism , Female , Humans , Intervertebral Disc Degeneration/enzymology , Lumbar Vertebrae/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Sacrum/enzymology , Sacrum/pathologyABSTRACT
We report an 11-year-old child with fracture of the distal clavicle who was denied conservative treatment because the medial end of the clavicle was anchored into the trapezius muscle fiber by an extreme posterior displacement. Surgical reduction was indicated.
