Ph.D Thesis

Ph.D StudentEviatar Tamar
SubjectThe Effects of IGFs and the Binding Protein IGFBP-3 on
MMPs in Articular Cartilage of Joints
DepartmentDepartment of Medicine
Supervisor MRS Erella Livne (Deceased)


An active balance between synthesis and degradation of cartilage matrix components takes place in healthy joints. In the chronic disease, osteoarthritis, this balance is disturbed. Degradation of the two main components, collagen and PGs, is carried out by matrix metalloproteinases (MMPs) in both normal and osteoarthritic cartilage. Insulin-like growth factor-I (IGF-I) has been documented as the major growth factor involved in the induction of cartilage matrix synthesis. The objective of this study was to examine the effects of IGF-I and IGFBP-3 on MMPs activity and expression in articular cartilage explants as related to aging and osteoarthritis. Articular cartilage of 3, 7, 12 and 18 month-old ICR mice was cultured in the presence or absence of IGFBP-3, followed by incubation with IGF-I, IGF-I together with IGFBP-3 or IGFBP-3 alone. Activity and expression of the various MMPs were evaluated in cultured explants and in the corresponding conditioned medium. The effect of IGF-I was increased by pre-incubation of the tissues with IGFBP-3. This treatment was found to be the most effective. The addition of IGF-I resulted in decreased activity of MMP-2 and MMP-9 in normal aging cartilage. Increased activity and expression of MMP-3 and MMP-13 mRNAs and proteins were apparent in OA and normal cartilage. It can be concluded that IGF-I should be carefully considered in therapeutic treatment of cartilage. IGF-I may possibly assist in maintaining healthy cartilage and preventing the initiation of OA by elevating the synthesis rate of PG and collagen type II and by reducing MMP activity. The contraindication exists in the presence of active OA where IGF-I would probably intensify rather than inhibit the process.