Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

Abstract

We recently found that injection of 2 mCi of yttrium 90 (90Y; -123,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.Although the use of radiation synovectomy for the treatment of refractory localized synovitis is becoming more common (l), little is known about the effects of this treatment on articular cartilage. Since cells that are most susceptible to the effects of radiation are generally those that exhibit a rapid rate of cell division (2), and chondrocytes in normal adult articular cartilage lack mitotic activity (3), radiation might be expected to have little effect on this tissue. In support of this, only minimal histologic alteration has been seen in cartilage following irradiation (2,(4)(5)(6), even with as much as 640,000 rads (6).We recently examined the effects of injection of yttrium 90 (90Y) into normal canine knees (7). While synovium from the irradiated knees exhibited extensive subintimal fibrosis and fibrin deposition, the histologic appearance of articular cartilage from these knees remained normal, suggesting that radiosynovectomy had not damaged the cartilage. Surprisingly, the rate of glycosaminoglycan (GAG) synthesis in articular cartilage from the irradiated knees was an average of 26% higher (ranging to 150% higher) than that in cartilage from the contralateral, nonirradiated knees. This raised the possibility that synovial ablation had stimulated cartilage GAG synthesis, either directly or by modulating the effects of a synovial factor(s) that influences cartilage GAG metabolism. Since direct effects of irradiation on the metabolism of

Effect of X-ray Irradiation on Articular Cartilage Mechanical Properties

“…But articular cartilage from adult humans or large animal species seems to degrade after exposure [24,29].…”

Impact of Therapeutic Irradiation on Healthy Articular Cartilage

“…Moreover, immediate radiation effects on extracellular matrix synthesis were minimal after two days, while marked decrease in glycosaminoglycan synthesis was observed 4 and 7 days after irradiation (37). However, cartilage glycosaminoglycan synthesis was reduced compared to nonirradiated cartilage, 24 h after 10-500 Gy doses of radiation in a model of normal canine articular cartilage (39). Inhibition of chondrogenesis measured using cartilage nodule production and Alcian blue staining, was observed in the first two days after irradiation of embryonic limb bud cells (40).…”

“…Radiation exposure induces an active degradation of cartilage, a reduced proteoglycan synthesis and more generally a decreased matrix production (40,39). Lowered Akt activation in irradiated chondrocytes is also involved in decreased matrix synthesis.…”

Animal models for osteoarthritis: processes, problems and prospects.

“…1 1115 Models directed towards articular cells Models directed towards inhibition of articular cells, predominantly chondrocytes, can be induced by physical agents such as freezing, electrolysis, or ionising radiation similar to that following intra-articular injection of 90Yttrium (90y). 123 Chemical agents such as intra-articular injection of the cytotoxic drugs Thiotepa, nitrogen mustard,'7 124 colchicine,'25 osmic acid,'26 or iodoacetate17 115 127 are capable of damaging articular cells selectively. For example, osmic acid, a fixative that has been administered intra-articularly for the therapy of rheumatoid arthritis, clinically and experimentally induces synovial fibrosis and functional impairment of residual synovial cells which contain osmic acid intracytoplasmic inclusions.…”