GENE-EXPRESSION OF NONCOLLAGENOUS BONE-MATRIX PROTEINS IN THE LIMB JOINTS AND INTERVERTEBRAL DISKS OF THE TWY MOUSE

The twy (tiptoe walking Yoshimura) mouse is an autosomal recessive mut ant manifesting multiple osteochondral lesions characterized by pathol ogic calcium deposition. To elucidate the pathophysiology of the limb joint lesions and the intervertebral disk lesions of the twy mouse, we assessed the mRNA expression of noncollagenous bone matrix proteins s uch as osteocalcin, osteonectin, osteopontin, and matrix Gla protein ( MGP) by in situ hybridization, but only expression of MGP was observed in association with the pathologic calcium deposits in twy mice. Mild degeneration and abnormal growth of the cartilage in contact with the joint capsule was observed at 5 weeks in the articular cartilage of t he ankle joint of the twy mouse, and MGP gene expression was observed at the same time. Simultaneous growth of synovial membrane cells and r elatively undifferentiated articular cartilage cells in the knee joint , and of cartilage-like cells near the insertion of the cruciate ligam ent was observed in the twy mouse, and MGP gene expression was found t o be present at the same time. Hypertrophy of abnormally proliferated chondrocyte-like cells, which are different from fibrocartilaginous ce lls of the annulus fibrosus, was observed in the intervertebral disks of the twy mouse at 3 weeks of age, and MGP gene expression was noted at the same time. These findings suggest that abnormal expression of M GP plays a major role in the pathologic calcification of the twy mouse .