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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.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

Parker WL,Finnson KW,Soe-Lin H,Knaus P,Philip A

doi

10.1016/j.joca.2006.10.006

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

442-53

issue

4

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(06)00293-7

journal_volume

15

pub_type

杂志文章

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