Characterization of the Responses of Human Synovial Fibroblasts In Vitro

Abstract

<p>The synovial membrane (SM) is a specialized tissue which lines the joint capsule surrounding the interface between bone and cartilage. The intimal layer of the SM, a 1 to 2 cell thick layer of myeloid and mesenchymally-derived cells, has generally been characterized as the population of cells responsible for the secretion of synovial fluid (SF) and with maintaining structural stability within the capsule of diarthrodial joints.</p> <p>In pathological states, the SM is transformed into an aggressive tissue inundated by inflammatory cells and their soluble mediators. The intimal layer of the SM and its resident cells, Type A and Type B synoviocytes, undergo an alteration in phenotype during disease, particularly chronic joint inflammation. These synoviocytes expand in number and activity and have been demonstrated to be involved in part with the arthritic lesions associated with inflammatory joint disease. The purpose of this thesis is to illustrate that the human synovial fibroblast (HSF or Type B synoviocyte) is a dynamic cell both responding to and influencing its local environment. More specifically, it is documented that HSF activity is significantly affected by a host of locally produced soluble mediators released during arthritic diseases. In addition, HSF are shown to respond to their environment by possessing the capability to alter the activity of other inflammatory cells which are present in the joint milieu. We also show that the pathological state of the originating SM is significant in determining the response and activity of HSF. That is, HSF-derived from normal SM respond to some stimuli differently than do HSF derived from SM originating from diseased joints.</p>