These results suggest that collagenase injected intra-articularly digests cartilage directly and stimulates an inflammatory reaction of joint tissues at an early stage, and then cartilage degeneration proceeds. This experimental osteoarthritis is a useful animal model, since the cartilage degeneration is similar to the corresponding lesion in human osteoarthritis, and it is conveniently induced by a dose of collagenase lower than that of papain used, within a short period.

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Chronic topical treatment of rats with a new RARgamma-selective retinoid, ER36009, resulted in a significant reduction of epididymal white adipose tissue and a significant increase of interscapular brown adipose tissue without affecting food intake. ER36009 markedly decreased PPARgamma, 11beta-HSD1, and Bcl-2 mRNA levels, and increased Bax mRNA in white adipose tissue, while it upregulated UCP1 and UCP3 mRNAs in brown adipose tissue and UCP3 mRNA in gastrocnemial muscle. These results suggest that ER36009 has multiple effects on adipose tissue biology and the energy balance. Topically applied ER36009 may have potential for the treatment of obesity.

These data indicate that RARgamma, but not RXR, plays an important role in the improvement of the signs of photoaging, and so a specific RARgamma agonist might be superior to an RAR pan-agonist for clinical treatment. We conclude that ER36009 is a candidate for a potent anti-skin-aging agent.