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Introduction: Lubricin, a heavily
glycosylated proteoglycan, has provoked much enthusiasm amongst
investigators involved with orthopedic medicine. First described in what
have become seminal studies involving bovine synovial fluid; lubricin, an
endogenous product of the Proteoglycan-4 (PRG-4) gene, is now thought to
be the primary boundary lubricant of diarthrodial joints. As such,
lubricin has been shown to significantly reduce the frictional coefficient
in ambulating joints. The PRG-4 gene has also been implicated in the
autosomal recessive disorder camptodactyly-arthropathy-coxa
vara-pericarditis syndrome (CACP) in which PRG-4 mutations result in the
manifestations of precocious arthropathy, pericarditis and coxa vara.
Likewise, PRG-4 knock-out mice have demonstrated analogous joint pathology
as that seen in their CACP counterparts.
Student Project:
The student will test if lubricin is expressed within articular
and non -articular tissue. Lubricin mRNA transcripts are speculated to be
found in pericardium, peripleura, mesothelium and peritoneum. We will be
targeting these tissues as they are continuously exposed to frictional
forces, making them prime candidates for tissue adhesions and cell damage.
Lubricin may play a role in circumventing these untoward consequences in
healthy subjects due to its boundary lubricating ability. Justification
for investigation comes from the extra-articular manifestations seen in
CACP and the strikingly similar findings seen in studies involving PRG-4
knock-out mice. Compromised lubricin expression may contribute to the
intra- and extra-articular manifestations of CACP. |