This study provides a direct evidence of the role of mTOR and its downstream modulation of autophagy in articular cartilage homeostasis.

ObjectivesWe have previously shown that peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor, is essential for the normal growth and development of cartilage. In the present study, we created inducible cartilage-specific PPARγ knockout (KO) mice and subjected these mice to the destabilisation of medial meniscus (DMM) model of osteoarthritis (OA) to elucidate the specific in vivo role of PPARγ in OA pathophysiology. We further investigated the downstream PPARγ signalling pathway responsible for maintaining cartilage homeostasis.MethodsInducible cartilage-specific PPARγ KO mice were generated and subjected to DMM model of OA. We also created inducible cartilage-specific PPARγ/mammalian target for rapamycin (mTOR) double KO mice to dissect the PPARγ signalling pathway in OA.ResultsCompared with control mice, PPARγ KO mice exhibit accelerated OA phenotype with increased cartilage degradation, chondrocyte apoptosis, and the overproduction of OA inflammatory/catabolic factors associated with the increased expression of mTOR and the suppression of key autophagy markers. In vitro rescue experiments using PPARγ expression vector reduced mTOR expression, increased expression of autophagy markers and reduced the expression of OA inflammatory/catabolic factors, thus reversing the phenotype of PPARγ KO mice chondrocytes. To dissect the in vivo role of mTOR pathway in PPARγ signalling, we created and subjected PPARγ-mTOR double KO mice to the OA model to see if the genetic deletion of mTOR in PPARγ KO mice (double KO) can rescue the accelerated OA phenotype observed in PPARγ KO mice. Indeed, PPARγ-mTOR double KO mice exhibit significant protection/reversal from OA phenotype.SignificancePPARγ maintains articular cartilage homeostasis, in part, by regulating mTOR pathway.

ARC and CB were both effective for attenuation of CEHPSS, resulting in good to excellent outcomes with low morbidity and mortality. Residual shunting was suspected in a higher proportion of dogs treated with CB on the basis of abdominal ultrasonography results. However, further prospective randomized studies must be conducted with validated evaluation methods to verify this assumption.

Five modifications of a cricoarytenoid lateralization and two modifications of a thyroarytenoid lateralization laryngoplasty technique were evaluated for their effect on rima glottidis area. All procedures and evaluations were performed on canine cadaver larynges. Cricoarytenoid lateralization (CAL) techniques provided a greater increase of the size of the glottic opening than did any of the thyroarytenoid lateralization techniques. Cricoarytenoid and interarytenoid disarticulation associated with CAL did not significantly increase glottic size compared with normal. After disarticulation of the cricoarytenoid joint, there was no difference in glottic enlargement whether the suture was placed through the muscular process or through the articular facet of the arytenoid cartilage. Transection of the sesamoid band combined with cricoarytenoid diarticulation distorted the dorsal margin of the rima glottidis.