Cartilage intermediate layer protein expression in calcium pyrophosphate dihydrate crystal deposition disease

To elucidate the mechanisms of calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) in the meniscus, synovium, labrum, tendon, ligament, and soft tissue, we studied the expression of cartilage intermediate layer protein (CILP).

Histological sections and clinical data from 33 patients who fulfilled the criteria of Ryan and McCarty for CPPD were reviewed. Formalin fixed and paraffin embedded tissue sections of 33 patients with CPPDCD were stained with hematoxylin and eosin (H&E) and alizarin red S. Immunostaining was performed using affinity purified polyclonal antibody to synthetic peptide corresponding to the N-terminal sequence of the 61 kDa domain of porcine CILP.

The age of patients ranged from 49 to 89 years (median 73). The knee was the commonest site. Radiologically, almost all lesions exhibited fine, radiopaque, linear deposits in the meniscus, articular cartilage, and synovium or joint capsule. Histopathologically, all cases showed deposits of birefringent monoclinic or triclinic crystals, which were visualized by polarized light microscopy with a red analyzer filter. In alizarin red S staining, more numerous crystals were observed than in H&E staining. Crystal deposition was usually associated with adjacent variable amounts of hypertrophic and/or metaplastic chondrocytes in each type of tissue. Variable intensity of CILP immunostaining was found in deposits of each lesion. Hypertrophic/metaplastic chondrocytes in and around CPPD deposits were also positive for CILP. Small cartilaginous islands remote from the CPPD deposits exhibited a weak positivity for CILP. In addition, weakly positive chondrocytes were noted in a transitional zone between cartilaginous islands with and without the deposits. In addition to cytoplasmic immunoreactivity, immunostaining for CILP was observed in the pericellular fibrous matrix.

Hypertrophic or metaplastic chondrocytes characteristic of CPPDCD may be directly involved in the formation of CPPD crystals. Our study suggests that increased CILP expression was closely associated with CPPDCD, and might play a role in promoting CPPD crystal formation.