ABSTRACT
The deposition of basic calcium phosphate (BCP) and calcium pyrophosphate
dihydrate (CPPD) crystals in articular tissues is probably an under-recognized
event. Clinical observations indicate that exaggerated and uniquely distributed
cartilage degeneration is associated with these deposits. Measurements of putative
markers of cartilage breakdown suggest that these crystals magnify the
degenerative processes that occur in osteoarthritis. Recent studies suggest that
there are three potential mechanisms by which crystals can cause degeneration.
The first two involve the induction of mitogenesis in synovial fibroblasts and the
secretion of matrix metalloproteinases by cells that phagocytose these crystals.
The third potential mechanism involves changes in joint biomechanics. Articular
calcification may lead to altered loading of the joint causing injury to the cartilage
matrix, which fails under normal loading, and chondrocytes respond by
elaborating matrix metalloproteinases and developing inappropriate repaired
responses (1,2). Therefore, the general therapeutic strategy should include
formulation of compounds that block the formation of new crystals by inhibition of
nucleation, formation, and growth of the primary crystals and can also target
crystal-stimulated intracellular responses. Unfortunately, more definitive inves-
tigations of therapeutic agents are impeded by the lack of a suitable animal model
for studying non-inflammatory aspects of crystal deposition, and the slow pace of
degeneration (3,4).
