In vivo expression of stromelysin in synovium and cartilage of rabbits injected intraarticularly with interleukin-1 beta.
OBJECTIVE
To examine the in vivo expression of the matrix metalloproteinase stromelysin in the synovium and articular cartilage of rabbits injected intraarticularly with recombinant human interleukin-1 beta (IL-1).


METHODS
The direct isolation of messenger RNA (mRNA) from articular cartilage without the prior isolation of chondrocytes is described. The in vivo expression of stromelysin was examined at the mRNA level by Northern blot analysis, and at the protein level by in situ immunolocalization and by enzyme-linked immunosorbent assay.


RESULTS
In the synovium of IL-1-injected joints, stromelysin mRNA levels were highest at 4 hours and declined to background levels within 24 hours. In the cartilage of IL-1-injected joints, stromelysin mRNA was elevated at 4 hours and continued to increase until 8 hours, before declining. Stromelysin mRNA expression preceded a similar increase in stromelysin protein levels in both synovium and cartilage.


CONCLUSIONS
Intraarticular injection of IL-1 induced the endogenous expression of stromelysin mRNA and protein in both synovium and cartilage. The kinetics of stromelysin expression correlated well with the accumulation of stromelysin and proteoglycan in synovial fluids. Therefore, the de novo synthesis of stromelysin in cartilage may have contributed to the loss of proteoglycan from that tissue.
Hutchinson
N I
NI
Department of Immunology and Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065.
Lark
M W
MW
MacNaul
K L
KL
Harper
C
C
Hoerrner
L A
LA
McDonnell
J
J
Donatelli
S
S
Moore
V
V
Bayne
E K
EK
D000818:Animals; D002358:Cartilage, Articular / Q000201:enzymology*; D005260:Female; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013582:Synovial Fluid / Q000201:enzymology / Q000378:metabolism; D013583:Synovial Membrane / Q000201:enzymology*
D007375:Interleukin-1; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3