Transforming growth factor beta 1 regulates tissue inhibitor of metalloproteinases-1 expression in differentiated human articular chondrocytes.
OBJECTIVE
To investigate the role of interleukin-6 (IL-6) and transforming growth factor beta 1 (TGF beta 1) in the regulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) synthesis in human articular chondrocytes.


METHODS
Articular cartilage was obtained from human knee joints 24 hours after death. Chondrocytes were isolated by collagenase digestion and embedded in low-gelling-temperature agarose. After stimulation by cytokines, total RNA was isolated and analyzed by Northern blotting. TIMP-1 protein levels were determined using a competitive enzyme-linked immunosorbent assay.


RESULTS
Human chondrocytes in agarose culture expressed messenger RNA (mRNA) for the IL-6 receptor (gp80) and its signal-transducing subunit gp130. In contrast to the findings in a previous study, IL-6 did not stimulate TIMP-1 expression in these cells, whereas TGF beta 1 was an important inducer of TIMP-1 mRNA and protein synthesis.


CONCLUSIONS
Our findings suggest that TGF beta 1 has a protective effect on the extracellular matrix of human articular chondrocytes.
Günther
M
M
Institut für Biochemie, Rheinisch-Westfälischen Technischen Hochschule (RWTH), Aachen, Germany.
Haubeck
H D
HD
van de Leur
E
E
Bläser
J
J
Bender
S
S
Gütgemann
I
I
Fischer
D C
DC
Tschesche
H
H
Greiling
H
H
Heinrich
P C
PC
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D006023:Glycoproteins; D015850:Interleukin-6; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D008666:Metalloendopeptidases