This study defines gross, histopathologic, and radiologic changes associated with intervertebral disc degeneration in a spontaneously occurring form of the disease in aging sand rats (Psammomys obesus). Sand rats (male/female) fed lab chow supplemented with desert salt bush were sacrificed at periods of 3-30 months. Lateral thoracolumbar spine films were obtained. At sacrifice, spines were surgically exposed and gross findings were recorded; after fixation/decalcification, histopathologic studies were carried out using hematoxylin and eosin, and Safranin-O with fast green counterstain. Metabolic studies included correlations of pathologic and radiologic findings with blood glucose and insulin levels. Disc-space narrowing and subchondral endplate sclerosis increased radiologically with age, with more severe lower lumbar disc lesions. Ligamentous calcifications ventral to involved discs and caudal vertebrae were common. Disc thinning and anterior vertebral bony/cartilaginous spurs were more marked with age. Microscopy revealed loss of nucleus pulposus physaliform cells, chondrocyte replication, disc necrosis, and ossification. Hyperglycemia with and without hyperinsulinemia was common. No statistically significant differences in pathologic findings were noted, neither in diabetic versus nondiabetic nor in hyperinsulinemic animals. The sand rat is a model of disc degeneration; similarities with possible overlap with diffuse idiopathic skeletal hyperostosis syndrome were noted.
The finding that IGF-1 is present in levels about one-half as great in SF as compared with serum suggests that IGF-1 may be produced in lesser amounts or is utilized by the patient in customary joint function. The finding that GH is present in SF at values twice as high, or more, of serum levels in inflammatory arthritides suggests that GH may play a role in the pathophysiology of arthritic disorders.
Alterations in the integrity of the extracellular matrix play an important role in osteoarthritis. Matrix crosslinks in articular cartilage of the knee were studied in partially meniscectomized rabbits to compare changes due to osteoarthritis with those occurring during aging. Pyridinoline, a lysyl oxidase-initiated crosslink, and pentosidine, a crosslink formed by the Maillard/glycation reaction, were assayed separately on reverse-phase high performance liquid chromatography. A significant increase in the percentage of insoluble collagen was observed in normal 12-month-old rabbits compared with the levels in 3-month-old animals, whereas osteoarthritis was associated with a shift toward more soluble fractions. Total pyridinoline content did not change with age or osteoarthritis. Total pentosidine, however, increased significantly with age but remained constant with osteoarthritis. Analysis of the distribution of crosslinks among solubility fractions indicated a significant shift of pyridinoline from the pepsin-released fraction to the insoluble fraction with osteoarthritis, but no changes were observed with age. Pentosidine distribution shifted toward the pepsin-released fraction in osteoarthritis, with a shift toward the insoluble fraction with age. Because of the low levels of pentosidine present, its precise location, whether collagenous or noncollagenous, remains unclear. However, since pentosidine represents a marker for the overall Maillard reaction, the results of our studies support a role for Maillard reaction products in the aging of extracellular matrix. The shift of pentosidine toward more soluble fractions suggests the presence of matrix degradation and repair in osteoarthritis.
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