EXPRESSION OF PROTEOGLYCAN mRNA IN PATIENTS WITH PAINFUL CLICKING AND CHRONIC CLOSED LOCK OF THE TMJ
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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. www.indiandentalacademy.com
• 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. www.indiandentalacademy.com
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. www.indiandentalacademy.com
• 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. www.indiandentalacademy.com
• 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. www.indiandentalacademy.com
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 www.indiandentalacademy.com
• 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. www.indiandentalacademy.com
â&#x20AC;˘ Exclusion criteria : other TMJ diseases dentofacial deformity major jaw trauma previous TMJ surgery previous steroid injection in the TMJ â&#x20AC;˘ The disc and the posterior disc attachment specimens were separated immediately and stored on RNA later at -20 c until processed. www.indiandentalacademy.com
RESULTS
â&#x20AC;˘ 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. â&#x20AC;˘ 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. www.indiandentalacademy.com
• 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. www.indiandentalacademy.com
â&#x20AC;˘ 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. â&#x20AC;˘ The relative fluorescence values for fibromodulin and versican varied considerably within the groups, a variability that did not seem to correlate to group identity. www.indiandentalacademy.com
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 www.indiandentalacademy.com primarily affects the disc margins.
â&#x20AC;˘ 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. â&#x20AC;˘ This hypothesis for the development of CL in PC does not preclude other mechanisms in single cases. www.indiandentalacademy.com
â&#x20AC;˘ 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. â&#x20AC;˘ 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. www.indiandentalacademy.com
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