Abstract 48

TRAIL and TRAIL Receptor Expression by Chondrocytes from Degenerate and Healthy Cartilage in Osteoarthritis.

Anak Agung Sagung Sri Kencana Dharmapatni¹, David M. Findlay ², Andreas Evdokiou ², Holding C¹, Wallwork M³ David R.Haynes¹

¹ Dept. of Pathology, The University of Adelaide, South Australia, Australia
² Dept. of Orthopaedics and Trauma, The University of Adelaide, and Hanson Institute, South Australia, Australia
³ Adelaide Microscopy, The University of Adelaide, South Australia, Australia

This study investigated the expression of Tumour Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) and TRAIL receptors on chondrocytes and cartilage from patients with OA. We also examined the effect of TNF _.and IL1_ on the expression of TRAIL and TRAIL receptors on chondrocytes. The sensitivity of chondrocytes to TRAIL induced apoptosis was also investigated.

Tissue was taken from areas of healthy and degenerate cartilage from patients undergoing total knee replacement. Immunohistochemical detection of TRAIL and TRAIL receptors was carried out on frozen sections of cartilage. Immunofluorescence staining was carried out on cultured chondrocytes. Apoptotic cells after treatment with soluble TRAIL was visualised using DAPI (4',6 diamidino-2 phenylindole dilactate) staining. Cell viability was measured by crystal violet staining.

TRAIL,OPG and TRAIL R4 was expressed in both healthy and degenerate cartilage. Immunoflourescence staining confirmed that chondrocytes constitutively express TRAIL,TRAIL R4 and OPG. Treatment with TNF. but not IL1_, upregulated TRAIL expression. Both IL1_ and TNF_ upregulated expression of TRAIL R4 and OPG. Approximately 10-25 % of the chondrocytes demonstrated apoptosis after TRAIL treatment.

TRAIL can be detected in chondrocytes and both degenerate and healthy part of cartilage from patients with OA. However, only small amount of chondrocytes undergo apoptosis after induction with soluble TRAIL. This may be due to the expression of the decoy receptors OPG and TRAIL R4. These findings indicate that chondrocyte apoptosis mediated by TRAIL may have a role in the degeneration of cartilage in OA but the importance this in OA is yet to be determined.

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