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Departments
of Biochemistry (SC, KEK, AAC), Orthopedic Surgery (KEK), and Anatomy (AAC),
Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago,
Illinois |
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SUMMARY: The objectives
of this study were the following: (a) describe the appearance of histopathologic
changes observed in human articular cartilage from the knee and ankle joints
of organ donors with no symptomatic joint disease; (b) compare by in situ
hybridization mRNA expression of six matrix metalloproteinases (MMP) in
these cartilages; (c) compare MMP mRNA expression with the histology of
the cartilage; and (d) test whether the effect of interleukin-1[beta] (IL-1[beta])
on the MMP mRNA expression could be detected with in situ hybridization.
Human articular cartilages from the knee (tibiofemoral) and ankle (talocrural)
joints of 41 different donors (aged 18 to 84 years) were obtained through
the Regional Organ Bank of Illinois. The microscopic appearance of the cartilages
was graded on a histopathologic scale from 0 to 13 with the highest grade
representing severely damaged cartilage. In situ hybridization was performed
using oligonucleotide probes to three collagenases (MMP-1, MMP-8, MMP-13),
gelatinase A (MMP-2), stromelysin (MMP-3), and matrix type-1 metalloproteinase
(MMP-14). Cartilages from some donors were cultured with IL-1[beta] and
then analyzed for MMP expression using in situ hybridization. The histopathology
grades of the cartilages from the asymptomatic donors covered the entire
scale even in the ankle. Based on their grades, the cartilages were described
as either normal (grades 0 to 5) or damaged (grades 6 to 13). The cartilages
contained message for all six MMP tested with no detectable differences
in expression of MMP-1, -2, -13, and -14 between the normal and damaged
cartilages. However the expression of MMP-3 and MMP-8 was elevated in the
damaged cartilages. In normal knee cartilage, mRNA expression of MMP-3 and
MMP-8 was low, whereas in normal ankle cartilage, MMP-8 expression was below
the detection limit. MMP-3 and MMP-8 message was up-regulated in the damaged
cartilage from both joints, or if the tissue was cultured in the presence
of IL-1[beta]. From this study we conclude the following: (a) similar histopathologic
changes occur in both knee and ankle cartilages; (b) MMP-1, -2, -13, and
-14 are constitutively expressed in adult human cartilage; and (c) only
up-regulation of mRNA expression of MMP-3 and MMP-8 could be detected with
naturally occurring cartilage damage and IL-1[beta] induction. |
