RHO-SUBFAMILY GTPASES IN CARTILAGE HOMEOSTASIS:

Cartilage cells lose their ability to respond to growth factors, such as insulin-like growth factor-I (IGF-I), during the natural process of aging and in arthritis. This is inopportune given the number of studies that we and others have performed demonstrating the robust ability of IGF-I to enhance normal cartilage synthesis and to protect cartilage from degrading enzymes.

Our laboratory has several on-going projects to try and determine the nature of this growth factor resistance. More specifically, we are studying the intracellular signaling cascades induced by IGF-I in normal and arthritic cells with primary focus on the signaling molecules Cdc42, Rac, and RhoA; all members of the Rho-subfamily of GTPases. These signaling molecules control several physiologic cellular processes and they determine the shape (morphology) of cells. Importantly for cartilage cells, morphology has been directly linked to synthesis of normal cartilage proteins.

Cartilage cells stained for Cdc42 signaling protein (green dots) reveals concentration of the signaling protein next to the nucleus in the golgi apparatus (arrow).

Studies investigating the link in signaling pathways between IGF-I and Cdc42/Rac/Rho will further our understanding of the molecular mechanisms of IGF-I resistance in cartilage cells and direct us toward interventional therapies to retain their responsiveness to this repair-enhancing growth factor.

Laboratory Member and Cornell University Summer Leadership Program student, James Weemhoff studying changes in Rho protein expression in cartilage during aging and in response to IGF-I treatment.

Funded by: NIH AG00905