title: Expression and function of TbetaRII-B, a variant of the type II TGF-beta receptor, in human chondrocytes.
abstract: OBJECTIVE
  Transforming growth factor-beta (TGF-beta) has profound effects on chondrocyte proliferation and matrix production, and dysregulation of TGF-beta action has been implicated in osteoarthritis. The mechanisms by which the diverse actions of TGF-beta are regulated in chondrocytes are unclear. Although it is well documented that TGF-beta signaling is transduced by types I and II receptors, other TGF-beta receptors may play critical roles by regulating signaling receptor activity. Our objective was to examine the expression of TbetaRII-B, a splice variant of the type II TGF-beta receptor, and to analyze its role in regulating TGF-beta signaling in human chondrocytes.
  
  
  METHODS
  TbetaRII-B expression was examined in human cartilage tissue specimens, human chondrocyte cell lines C28/I2 and tsT/AC62, and human primary chondrocytes by Western blot and reverse-transcriptase-polymerase chain reaction. Ligand binding and heteromerization of TbetaRII-B with other TGF-beta receptors on the cell surface were analyzed by affinity labeling, immunoprecipitation, and two-dimensional SDS-PAGE. Regulation of TGF-beta responses by TbetaRII-B was determined by examining Smad2 phosphorylation, Smad3-specific signaling, transcriptional activity, and type II collagen levels.
  
  
  RESULTS
  TbetaRII-B is expressed in normal and osteoarthritic human cartilage. Furthermore, it is a dynamic component of the TGF-beta receptor system in human chondrocytes, forming heteromeric complexes with the types I and II TGF-beta receptors, betaglycan and endoglin. Importantly, overexpression of TbetaRII-B leads to enhanced TGF-beta signaling and responses in chondrocytes.
  
  
  CONCLUSIONS
  These results suggest that TbetaRII-B may play a key role in the regulation of TGF-beta action in human chondrocytes.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, Quebec, Canada.
authors.forename: W L
authors.initials: WL
authors.lastname: Parker
authors.forename: K W
authors.initials: KW
authors.lastname: Finnson
authors.forename: H
authors.initials: H
authors.lastname: Soe-Lin
authors.forename: P
authors.initials: P
authors.lastname: Knaus
authors.forename: A
authors.initials: A
authors.lastname: Philip
mesh_terms: D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II