GEP: A Novel Chondrogenic Growth Factor and Target in Arthritis

Arthritis is a degenerative joint disease, occurring primarily in the senior population, which currently affects more than 46 million individuals in the United States. Typical clinical symptoms are pain and stiffness, particularly after prolonged activity. In industrialized societies, arthritis is the leading cause of physical disability, increased health care usage, and impaired quality of life. The impact of arthritic conditions is expected to grow as the population both increases and ages in the coming decades.

Despite its prevalence, the precise pathogenesis and progression of arthritic diseases are not known.. Evidence is accumulating that demonstrates the significance of inflammatory cytokines and growth factors in osteoarthritis. The destruction of cartilage and bone in arthritic joints is thought to be mediated by excessive cytokine activities and imbalance between inflammatory cytokines and their physiological antagonists.

Dr. Liu’s studies discovered granulin/epithelin precursor (GEP) as a novel growth factor that plays an essential role in cartilage formation. More importantly, this growth factor directly associates with TNF (tumor necrosis factor) receptors and may act as a naturally-occurring antagonist of TNF-alpha, the central inflammatory cytokine in arthritis. These discoveries and the proposed studies will better explain the destructive processes that occur in patients with arthritis. Successful completion of the proposed research will not only improve understanding of the molecular mechanisms by which growth factors and cytokines control cartilage development and osteoarthritis, but may also lead to the development of a new biological treatment alternative to surgical and pharmaceutical treatments for arthritis.