טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentCarmel Julia
SubjectInvolvement of Cytokins and Growth Factors in Degradation
and Synthesis in Articular Cartilage
DepartmentDepartment of Medicine
Supervisor Ms. Erella Livne (Deceased)


Abstract

Interleukin 1b (IL-1b) was suggested to be involved in the destruction of joint tissues. Matrix metalloproteinases (MMPs) are the major proteinases involved in the pathologic degradation of cartilage matrix. In contrast to IL-1, TGF-b1 induces cell proliferation and PG synthesis in cartilage and stimulates cartilage repair.

The purpose of the present study was to test the in vitro effects of IL-1 on metabolic markers and on MMPs activity in articular cartilage and to test the ability of TGF-b to diminish these effects.

Temporomandibular (TMJ) condyle and knee joint cartilages (femoral condyle and tibial plateau) of 3-month-old ICR mice were dissected and cultured in BGJb medium in the presence 50-3000 U/ml (0.25-25 ng/ml) of IL-1b for 3&6 days. In some groups TGF-b1 was added after 3 days of exposure to IL-1b so that the last 3 days the these groups were treated by combination of IL-1 and TGF-b1.

Results indicated that IL-1b caused significant reduction of 35S-sulfate and 3H-thymidine incorporation in TMJ and tibial cartilages, and that TGF-b1 partly reversed this effect. IL-1b induced elevation of MMP-2, MMP-9 and MMP-13 activity in homogenate and medium of all cartilages tested. It has been also shown that TGF-b reduced MMPs activation caused by IL-1b treatment only in tissue homogenate but not in culture medium.

Morphology revealed cartilage destruction, cell reduction, atypical hypertrophy and loss of PG content under IL-1b effect that was partially restored after treatment by TGF-b. Additionally, effect of IL-1 was found to vary according to the different cartilages tested.

It is concluded that IL-1b stimulated catabolic activity in joint cartilages as shown by activation of MMPs, by reduction of cell proliferation and PG synthesis and by tissue destruction. TGF-b partially restored these effects.