Connective tissue, glycosaminoglycans, and diseases of the thyroid

Connective tissue imparts cohesion, strength, and form to the organs that it invests. It is comprised of several discrete cellular and noncellular components. The fibroblast and its more specialized derivatives (such as chondrocytes and osteocytes) elaborate and release several important molecules such as fibrous proteins (collagen), attachment proteins (fibronectin), glycoproteins, and ground substance. In this article we review the now abundant evidence that fibroblasts and their products are important mediators of some peripheral expressions of thyroid disease, including myxedema, pretibial dermopathy, thyroid acropachy, and ophthalmopathy of Graves’ disease. Our review concentrates predominantly on the glycosaminoglycans that comprise ground substance. The fibrous proteins are given less attention. The early prejudice that the ground substance and connective tissue in general were rather unimportant becomes apparent in a quote attributed to Von Haller (1), who in 1757 wrote that “it is evident that a considerable part of the human body consists of matter which for so many centuries has been regarded as rubbish.” Yet it is widely appreciated in contemporary biology that ground substance and the connective tissues play a crucial role in defining the microenvironment for specialized cells to function. They are important in cell attachment and cell-to-cell communication, and they influence the manner in which cells negotiate the extracellular milieu. A brief review of the physicochemical properties of the glycosaminoglycans that compose ground substance precedes the more detailed analysis of the impact that thyroid dysfunction can have on its synthesis and disposal.