Corticosteroid Inhibition of Human Articular Cartilage Biosynthesis
An early event in the development of osteoarthritis in a joint is proteoglycan loss from articular cartilage.86,87 Proteoglycans are very large molecules consisting of proteins with attached chains of polysaccharides called glycosaminoglycans. With the exception of hyaluronic acid, glycosaminoglycan units are sulfated, and consequently, highly negatively charged, allowing attraction and binding of water. Because of their great attraction for water, proteoglycans are viscous making them ideal for lubricating fluid in joints. The charges repel each other, which gives them an open structure and is space-filling. These biochemical traits contribute to the mechanical properties of proteoglycans in articular cartilage, such as absorption and distribution of compressive weight, and protect structures in the joints from mechanical damage. Therefore, any decrease in the tissue concentration of proteoglycans, compromises the functional properties of cartilage. Depletion of proteoglycans can result in fibrillation and degeneration of the articular cartilage.88-90 In all but severe cases of osteoarthritis, the chondrocyte response to proteoglycan depletion results in an increase in glycosaminoglycan synthesis.91-93 (See Figure 11.)
 In vitro studies of various corticosteroids, including dexamethasone, hydrocortisone, and betamethasone, have shown that they inhibit human glycosaminoglycan biosynthsis in a dose dependent manner.94-97 Ultimately when human articular cartilage is examined microscopically after intraarticular steroid injections, signs of degeneration are present.98,99 One human study examined the articular cartilage in the tempomandibular joint (TMJ) after two injections with triamcinolone and compared this to tempomandibular joints that did not receive any steroid injections. The researchers performed microscopic analysis examining the fibrous (top), cartilaginous, and subchondral bony layers of the articular cartilage tissue. The author summarized his results this way, “The results of this study revealed higher destruction to all layers of the joints that received intraarticular injection of triamcinolone acetonide, when compared to the group of joints, which received no steroid injections. This finding firmly supports the hypothesis; intraarticular injection of steroids acts in joints suffering from OA as a lytic agent with the potential to produce a pharmacological arthroplasty.”100 The author noted that his study revealed the complete loss of the fibrous layer in the steroid group in 84% of the specimens and that other studies showed a 100% loss.101,102 He explained it this way, “This is simply because the joints in this investigation received only two injections of steroids, meanwhile the joints in Poswillo’s study received six injections of steroids.”
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