OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of @entity571 ( @entity7441 ) in @entity35 , to assess the similarity of this model to @entity1 @entity7441 , and to identify genes and mechanisms leading to @entity7441 pathogenesis. METHODS: @entity7441 was surgically induced in 5 @entity35 by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the @entity7441 ( @entity7441 ), contralateral, and sham- @entity7441 knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including @entity794 , @entity1550 , @entity3531 , @entity26903 , Ptges, and @entity436 , were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of @entity7441 and sham- @entity7441 samples showed 1,619 differentially expressed probe sets with changes in their levels of expression > or = 1.5-fold, 722 with changes > or = 2-fold, 135 with changes > or = 4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in @entity1 @entity7441 included @entity1550 , @entity3531 , and @entity3840 , among others. Several dysregulated genes (e.g., @entity24109 , @entity15396 , and @entity29713 ) had been identified in our earlier microarray study of @entity1184 chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including @entity436 and @entity2842 , were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in @entity1 @entity7441 , supporting the relevance of newly identified genes and pathways to early @entity1 @entity7441 . We propose new avenues for @entity7441 pathogenesis research and potential targets for novel @entity7441 treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.

Global analyses of gene expression in early experimental XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity24109 :: ('5649', 'Gene') :: ['Reln'] @entity571 :: ('MESH:D010003', 'Disease') :: ['early osteoarthritis'] @entity29713 :: ('4053', 'Gene') :: ['Ltbp2'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophic'] @entity1550 :: ('4322', 'Gene') :: ['Mmp13'] @entity15396 :: ('5251', 'Gene') :: ['Phex'] @entity794 :: ('1280', 'Gene') :: ['Col2a1'] @entity26903 :: ('1075', 'Gene') :: ['Ctsc'] @entity2842 :: ('6347', 'Gene') :: ['Ccl2'] @entity3531 :: ('11096', 'Gene') :: ['Adamts5'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity7441 :: ('MESH:D056987', 'Disease') :: ['operated', 'OA'] @entity3840 :: ('5743', 'Gene') :: ['Ptgs2'] @entity436 :: ('7852', 'Gene') :: ['Cxcr4']
@entity571 :: (MESH:D010003,Disease) :: ['osteoarthritis']
