title: Rac1 signaling regulates CTGF/CCN2 gene expression via TGFbeta/Smad signaling in chondrocytes.
abstract: OBJECTIVE
  Connective tissue growth factor (CTGF) has been implicated in regulation of chondrocyte differentiation at multiple steps and has been implicated in the progression of diseases such as scleroderma and osteoarthritis. However, the pathways mediating the expression of CTGF/CCN2 and related factors in cartilage are not fully understood. We have previously shown that the Rho family of proteins and the actin cytoskeleton regulate both early and late chondrocyte differentiation.
  
  
  RESULTS
  Here we demonstrate that several CTGF/Cyr61/Nov (CCN) family members are differentially affected by either inhibition of actin polymerization (cytochalasin D treatment), promotion of actin polymerization (jasplakinolide treatment), inhibition of RhoA/rho kinase (ROCK) signaling (Y27632 treatment) and Rac1 signaling. We also show that the Smad site in the CTGF/CCN2 promoter is responsive to both Rac1 inhibition and cytochalasin D treatment, suggesting a role of TGFbeta/Smad signaling in mediating the effects of actin dynamics and Rac1.
  
  
  CONCLUSIONS
  Collectively, these data show that Rac1 and actin pathways control CTGF/CCN2 expression in chondrocytes which might be relevant to both skeletal development and associated diseases such as osteoarthritis.
authors.affiliation: CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Woods
authors.forename: D
authors.initials: D
authors.lastname: Pala
authors.forename: L
authors.initials: L
authors.lastname: Kennedy
authors.forename: S
authors.initials: S
authors.lastname: McLean
authors.forename: J S
authors.initials: JS
authors.lastname: Rockel
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Leask
authors.forename: F
authors.initials: F
authors.lastname: Beier