22 Introduction Tendon function, i.e., the transmission of tensile forces from muscle to bone, depends on the proper structure of the tendon 1 . In response to changes in loading and mobilization (i.e., exercise), as well as in the normal course of develop- ment, a tendon will be remodeled 2-4 . Its biochemistry and structure is then adjusted to facilitate its function under altered conditions 5,6 . Remodeling is not to be confused with repair, the replacement of damaged tissue with newly formed connective tissue. Current knowledge of remodeling mechanisms is incomplete and inconsistent but we know that components of the extracellular matrix (ECM) play crucial roles in this process 5 . The majority of macromolecules pres- ent in the extracellular matrix of tendons can be classified into three groups: (1) collagen, (2) proteoglycans, (3) glyco- proteins. Recent studies have shown that the assembly (i.e., fibrillogenesis) of the chief structural component of the ten- don, type I collagen, is regulated by proteoglycans (PGs) present in the ECM 7-12 . Structural integrity and normal mechanical function of the tendon depends on precise alignment of type I collagen fibrils. Those fibrils, identifiable by electron microscopy, are organized into fibers, bundles and fascicles at the light microscopic level. During chicken embryonal development, collagen fibrils are deposited first as discrete segments 10-30 Ìm long in extracytoplasmic spaces between tendon fibroblasts. The segments are assembled into fibers, and fibers are incorporated into the developing ECM 13 . PGs, most notably decorin, in the ECM modulate the formation and final sizes of the fibrils 3,10 . With exercise the turnover of mature collagen and colla- gen crosslinks increases 14,15 , large diameter fibrils are formed with increased packing density of fibrils 16 and increased ten- don stiffness 5 . Exercise also leads to changes in PG content 1 . Strenuous exercise in mature rodents or chickens leads to thickening of collagen fibrils and to an increase of the galac- tosamine-containing GAGs 17 . In contrast, immature tendons appear to respond to exercise with higher collagen turnover, reduced maturation of collagen 14 , and alterations in hyaluro- nan concentrations 18 . J Musculoskelet Neuronal Interact 2005; 5(1):22-34 Tendon proteoglycans: biochemistry and function J.H. Yoon 1 and J. Halper 2 1 Virginia Bioinformatics Institute, Virginia Polytechnic Institute, Blacksburg, VA, USA, 2 The Soft Tissue Center, Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA, USA Abstract Tendon remodeling occurs in response to changes in loading and mobilization. Though the normal mechanical function depends on precise alignment of collagen fibrils, it is proteoglycans that regulate collagen fibrillogenesis and thus, indirectly, tendon function. In this paper we discuss the basic biochemical structure of several members of two proteoglycans families. Decorin, biglycan, fibromodulin and lumican, all members of the small leucine-rich proteoglycans family, bind to collagen fib- rils and are active participants in fibrillogenesis. Aggrecan and versican, two members of large modular proteoglycans or lec- ticans, and their partner hyaluronan likely provide tendon tissues with a high capacity to resist high compressive and tensile forces associated with loading and mobilization. We present data from our laboratory showing that proteoglycans and gly- cosaminoglycan content increases not only with growth but also with loading of young avian gastrocnemius tendons. Specifically, an increase in the content of keratan sulfate, chondroitin sulfate and hyaluronan was observed. Moderate exer- cise for several weeks led not only to a further increase in total proteoglycans content but also to qualitative changes in pro- teoglycan make up. Keywords: Tendons, Proteoglycans, Glycosaminoglycans, Effect of Age and Loading Perspective Article Hylonome The authors have no conflict of interest. Corresponding ·uthor: Jaroslava Halper, M.D., Ph.D., Department of Patholo- gy, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA E-mail: jhalper@vet.uga.edu Accepted 28 January 2004