OBJECTIVE: @entity571 ( @entity571 ) is a serious disease of the entire joint, characterized by articular @entity528 , subchondral bone changes, osteophyte formation, and @entity1373 . Currently, there are no pharmaceutical treatments that can slow the disease progression, resulting in greatly reduced quality of life for @entity1 and the need for joint replacement surgeries in many cases. The lack of available treatments for @entity571 is partly due to our incomplete understanding of the molecular mechanisms that promote disease initiation and progression. The purpose of the present study was to examine the role of the nuclear receptor peroxisome proliferator-activated receptor    ( @entity3229  ) as a promoter of @entity528 in a @entity19 model of @entity571 . METHODS: @entity19 chondrocytes and knee explants were treated with a pharmacologic agonist of @entity3229   ( @entity29852 ) to evaluate changes in gene expression, histologic features, and matrix glycosaminoglycan breakdown. In vivo, @entity3229   was specifically deleted from the cartilage of @entity19 . Histopathologic scoring according to the @entity571 Research Society International (OARSI) system and immunohistochemical analysis were used to compare mutant and control @entity19 subjected to surgical destabilization of the medial meniscus (DMM). RESULTS: In vitro, @entity3229   activation by @entity29852 resulted in increased expression of several proteases in chondrocytes, as well as aggrecan degradation and glycosaminoglycan release in knee joint explants. In vivo, cartilage-specific @entity3229  -knockout @entity19 did not display any @entity245 but showed marked protection in the DMM model of @entity571 (as compared to control littermates). OARSI scoring and immunohistochemical analyses confirmed strong protection of mutant @entity19 from @entity38094 -induced @entity528 . CONCLUSION: These data demonstrate a catabolic role of endogenous @entity3229   in @entity571 and suggest that pharmacologic inhibition of @entity3229   is a promising therapeutic strategy.

Peroxisome proliferator-activated receptor    promotes the progression of XXXX in a @entity19 model.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity3229 :: ('19013(Tax:10090)', 'Gene') :: ['PPAR'] @entity571 :: ('MESH:D010003', 'Disease') :: ['OA', 'Osteoarthritis', 'posttraumatic OA'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mouse', 'mouse'] @entity1373 :: ('MESH:D006965', 'Disease') :: ['synovial hyperplasia'] @entity245 :: ('MESH:D002658', 'Disease') :: ['abnormalities of skeletal development'] @entity38094 :: ('CHEBI:67107', 'Chemical') :: ['DMM'] @entity29852 :: ('MESH:C425931', 'Chemical') :: ['GW501516'] @entity528 :: ('MESH:D009410', 'Disease') :: ['cartilage degeneration']
@entity571 :: (MESH:D010003,Disease) :: ['posttraumatic osteoarthritis']
