TSG-6 expression in human articular chondrocytes. Possible implications in joint inflammation and cartilage degradation.
OBJECTIVE
The hyaluronan-binding protein TSG-6 (tumor necrosis factor-stimulated gene 6) forms a stable complex with the serine protease inhibitor, inter-alpha-inhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examines the expression of TSG-6 in human articular chondrocytes and cartilage.


METHODS
Human articular chondrocytes and cartilage explants were stimulated with cytokines, growth factors, and other agents. TSG-6 expression was analyzed by imaging-assisted Northern and Western blotting.


RESULTS
TSG-6 messenger RNA (mRNA) expression was upregulated by cytokines and growth factors, predominantly interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), platelet-derived growth factor AA (PDGF-AA), and transforming growth factor beta 1 (TGF beta 1). TSG-6 mRNA induction by TGF beta 1 was delayed as compared with IL-1beta. Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG-6 mRNA nor did it affect IL-1 beta-induced transcript levels. TSG-6 mRNA induction may involve several signal transduction pathways. The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C (PKC)-mediated signaling. In contrast, PKA- and Ca- dependent signals are only marginally involved as messengers leading to increased TSG-6 levels after IL-1beta and TNF alpha treatment. In chondrocyte and cartilage organ cultures, both free TSG-6 (35 kd) and the complex with inter-alpha-inhibitor (120 kd) were present and upregulated by IL-1 beta, TNF alpha, or TGF beta 1.


CONCLUSIONS
Chondrocytes are a source of TSG-6 which may play a role in cartilage remodeling and joint inflammation.
Maier
R
R
University of California, San Diego, La Jolla 92093-0663, USA.
Wisniewski
H G
HG
Vilcek
J
J
Lotz
M
M
D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; C072273:TNFAIP6 protein, human