Role of cytokines and chemokines in cartilage and bone destruction in arthritis

Abstract

Cytokines are nonstructural proteins or glycoproteins that function as messengers between cells and regulate cell-cell interactions in diverse physiologic processes including embryonic development and organogenesis, cell growth and differentiation, immunoregulation and tissue remodeling and repair. Cytokines were originally identified according to the cells of origin and/or the biologic effect on target cells. Molecular cloning and characterization of gene products have permitted more rigorous classification of cytokines and receptors into families based on gene and protein structure. Systematic examination of the full spectrum of the biologic activities of individual cytokines and their family members reveals that cytokines tend to work together in networks that frequently consist of members of multiple cytokine families. Within cytokine networks, the activities of individual factors are often pleiotropic and there is considerable redundancy and overlap in their effects. In part, this is related to the use of common receptor subtypes and post-receptor signal transduction pathways among family members. Dysregulation of the activity or production of cytokines also play a critical role in the pathogenesis of a variety of pathologic processes including inflammatory disorders such as rheumatoid arthritis (RA). This manuscript will review the role of cytokines in the pathogenesis of joint diseases with a focus on their role in cartilage and bone remodeling. Included in the review will be an examination of the role of the chemokines in regulating the function of cartilage and bone cells. The discussion will use rheumatoid arthritis (RA) as a paradigm of inflammatory joint disease. In this condition, immune-mediated synovial inflammation results in progressive destruction of articular cartilage and loss of articular and peri-articular bone, and there is strong evidence supporting a pivotal regulatory role for cytokines in the initiation and perpetuation of the joint inflammation in this inflammatory joint disorder.