Expression of proteoglycan m rna in patients with painful clicking and chronic closed lock of the tmj /certified fixed orthodontic courses by Indian dental academy

EXPRESSION OF
PROTEOGLYCAN mRNA IN
PATIENTS WITH PAINFUL
CLICKING AND CHRONIC
CLOSED LOCK OF THE TMJ

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INDIAN DENTAL ACADEMY
Leader in continuing dental education


ABSTRACT

• RT-PCR was used to analyze the expression
of a series of mRNAs coding for
proteoglycans aggrecan, versican, biglycan,
decorin, fibromodulin and also hyaluronan
synthase 1 in specimens obtained during
disectomy of the TMJ in pts with unilateral
signs and symptoms of chronic closed lock
and painful clicking.
• Regarding the disc, aggrecan expression
was higher in pts with chronic closed lock.
As for the post disc attachment specimens,
the pts with chronic closed lock showed a
tendency of higher expression of biglycan
and hyluronan synthase 1.

• The degredation of matrix in pts with
chronic closed lock of the TMJ seems not
to be caused by areduced synthesis and
the degenerative process seen in these
pts is one with low turnover similar to the
situation in primary osteoarthrosis of
hyaline cartilage.
• The results indicate that any treatment
should intervene early in the disease
process of chronic closed lock in order to
prevent the development of a
degenerative process.

INTRUDUCTION

• TMJ internal derangement is the most common TMJ
affliction treated surgically.
• From a clinical point of view internal derangement of the
TMJ has two expressions: painful clicking (PC)
chronic closed lock (CL)
• Later being associated with osteoarthrosis (OA)
• OA is a chronic , principally non inflemmatoory
degenerative condition of the articular cartilage where
one of the earliest changes is a loss of proteoglycans
(PGs) from the tissue matrix.
• In a recent study comparing PC and CL pts , the later
showed a substantial loss of PGs from the affected disc.
• PGs create a swelling pressure in the tissue, necessary
for their ability to distribute point load.

• When amount of PGs diminished in the TMJ
disc, there was a corresponding loss in the
posterior disc attachment too.
• The fact that all pts with CL had such
degenerative changes in both tissues, i.e., that
none had changes limited only to the disc
tissues, indicate that the losses in both tissues
are components of the same degenerative
process, and it may be that the alterations in the
posterior attachment are of pathogenic
importance for the development of chronic
closed lock.
• In OA the diminished amount of PGs can
depend either on decreased synthesis,
increased degradation, or both.

• During secondary OA, following experimental
perforation of TMJ disc with incongruence of the
joint surface, increased degradation is
paramount in the rapidly progressing OA. On the
other hand, in primary OA, the cartilage matrix
degradation is usually preceded by enhanced
synthesis of PGs , probably as a response to
increased load.
• In this study the expression of the major PGs
giving the fibrous cartilage matrix an osmotic
pressure aggrecan and the collagen fiber
associated small PGs-biglcan, decorin and
fibromodulin- as well as hyaluronan synthase 1
(HAS-1),hyluronan being essential for anchoring
of the major PGs in the matrix.

MATERIALS & METHODS
• During TMJ disectomy, disc specimens including
the anterior part of the posterior disc attachment
were obtained from 8 consecutive pts( 7
females) with clinical diagnosis of CL
• Case history of sudden painful reduction of
mouth opening and reduced mouth opening
• And clinical findings of max mouth opening
(<40mm) and reduced protrusion(<8mm) and
tomographic signs of OA (erosion, sclerosis or
flattening of the articular surfaces).
• The mean age of pts was 39.8 yrs

• For comparison, biopsies were taken in
the same manner as for the CL pts in 7
consecutive pts (5 females) with the
clinical diagnosis of PC :painful TMJ
clicking and no radiographic signs of OA
on the preoperative tomograms.
• The mean age of these pts was 37.9 yrs.
• All the pts had been treated non surgically
for at least 6 months with out success.

• Exclusion criteria :
other TMJ diseases
dentofacial deformity
major jaw trauma
previous TMJ surgery
previous steroid injection in the TMJ
• The disc and the posterior disc attachment
specimens were separated immediately and
stored on RNA later at -20 c until processed.

RESULTS

• All PG-related genes studied gave distinct
amplimer bands, and with the cycle
combinations used both anlyte and control
bands were unsaturated and within the
selected ratio interval.
• The number of cyclic necessary to detect
analyte cDNAs was generally larger than
that needed when analyzing cDNAs from
the cultured cells with the same primers
4,6 but of the same magnitude as those
used when analyzing similarly prepared
cDNA from aortic tissue.

• The relative fluoresence of these genes were
similarly expressed in the different groups,
while in some cases there was considerable
inter-individual variability.
• In the discs there was a significant increase
of aggrecan expression in CL group when
comparing tissues from PC and cl patients.
• For biglycan, fibromodulin and versican,
there was a considerable inter-individual
variability.

• In the post disc attachment tissue the CL
group exhibited slightly increased
expression of HAS-1 and biglacan
although the differences were not
significant at the chosen levels.
• The relative fluorescence values for
fibromodulin and versican varied
considerably within the groups, a
variability that did not seem to correlate to
group identity.

DISCUSSION
• It has been assumed that PC may
precede a CL condition but it has also
been suggested that OA is a primary
cause preceding the internal
derangement.
• Long term fallow up of pts with PC has
shown that they, in a considerable
proportion have developed clinical signs
and symptoms of OA.
• Thus it can be speculated that when PC
develops into OA this degeneration will
primarily affects the disc margins.

• The rapid dissemination also to the
attachments will primarily affects the
physical properties of these looser
connective tissues. This will weaken the
disc attachments which in turn will allow
for a displacement of disc of sufficient
magnitude to cause CL.
• This hypothesis for the development of CL
in PC does not preclude other
mechanisms in single cases.

• Thus one should expect that any
degenerative lesion affecting the margins
of the disc may also cause CL even when
there is no previous history of PC.
• The obtained results in the study may also
indicate that any treatment should
intervene early in the disease process of
CL to prevent the displacement of
degenerative process.

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Leader in continuing dental education


Expression of proteoglycan m rna in patients with painful clicking and chronic closed lock of the tmj /certified fixed orthodontic courses by Indian dental academy

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Expression of proteoglycan m rna in patients with painful clicking and chronic closed lock of the tmj /certified fixed orthodontic courses by Indian dental academy