Notice that paracetamol (acetaminophen or Tylenol) did not inhibit GAG synthesis. The researchers noted that caution must be exercised in extrapolation from in-vitro (lab) to in-vivo (person) effects of NSAIDs, but it seems possible that some highly effective anti-inflammatory agents may produce adverse effects on cartilage integrity when employed during long-term treatment.77 Other researchers have confirmed NSAIDs’ inhibitory effect on proteoglycan synthesis and have commented that “…any drug that suppresses proteoglycan synthesis and impairs the ability of the chondrocyte to repair its damaged extracellular matrix, could potentially accelerate the breakdown of the articular tissue.”78, 79
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In selecting methods of restoring the damaged articular surface, it is important to distinguish articular cartilage repair from articular cartilage regeneration. Repair refers to the healing of injured tissues or replacement of lost tissues by cell proliferation and synthesis of new extracellular matrix. Unfortunately, repaired articular cartilage generally fails to replicate the structure, composition, and function of normal articular cartilage. Regeneration in this context refers to the formation of an entirely new articulating surface that essentially duplicates the original articular cartilage. Therefore, the best we can do at present is to repair chondral or osteochondral defects with functionally similar tissue.
Glossary | Linus Pauling Institute | Oregon State University
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Since normal articular chondrocytes produce very little PGE2 and osteoarthritic chondrocytes produce a lot of it through the COX-2 enzyme, it would make sense from a traditional medical point of view to attack arthritis pain from this angle. This is especially true since the over expression of the COX-2 protein (and thus increased PGE2 levels) plays an important role in many pathophysiolgic states, including systemic inflammation, fever, cancer, angiogenesis, Alzheimer’s disease, and inflammatory arthritis.96 Yes, in certain conditions inflammation is harmful, but it is a big leap to assume everywhere there is PGE2 it is harming tissue. The articular chondrocytes make PGE2 in response to injury to stimulate healing. Osteoarthritic cartilage spontaneously releases PGE2 in levels at least 50-fold higher than normal cartilage and 18-fold higher than normal cartilage stimulated with cytokines and endotoxin.97-100 The inflammation that occurs through PGE2 when a normal or osteoarthritic joint is injured is the body’s immune system response to try and get the joint injury repaired.101 When a person uses medications that block this response, while pain may be improved, the repair mechanisms for the joint are inhibited. The long-term consequences, of course can be an acceleration of the degenerative osteoarthritic process. (See Figure 16.) Long-term NSAID treatment not only blocks PGE2 production by direct inhibition of COX-2 activity but by down-regulating COX-2 synthesis.102