Development of tendon structure and function: Regulation of collagen fibrillogenesis

G. Zhang1, B.B. Young (1) *, Y. Ezura (1)**, M. Favata (2), L.J. Soslowsky (2), S. Chakravarti (3), D.E. Birk (1)

(1) Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA,
(2) McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA,
(3) Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

Current addresses:
*Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA,
**Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan

Abstract
In the tendon, the development of mature mechanical properties is dependent on the assembly of a tendon-specific extracellular matrix. This matrix is synthesized by the tendon fibroblasts and composed of collagen fibrils organized as fibers, as well as fibril-associated collagenous and non-collagenous proteins. All of these components are integrated, during development and growth, to form a functional tissue. During tendon development, collagen fibrillogenesis and matrix assembly progress through multiple steps where each step is regulated independently, culminating in a structurally and functionally mature tissue. Collagen fibrillogenesis occurs in a series of extracellular compartments where fibril intermediates are assembled and mature fibrils grow through a process of post-depositional fusion of the intermediates. Linear and lateral fibril growth occurs after the immature fibril intermediates are incorporated into fibers. The processes are regulated by interactions of extracellular macromolecules with the fibrils. Interactions with quantitatively minor fibrillar collagens, fibril-associated collagens and proteoglycans influence different steps in fibrillogenesis and the extracellular microdomains provide a mechanism for the tendon fibroblasts to regulate these extracellular interactions.

Keywords: Tendon, Development, Collagen Fibril Formation, Matrix Assembly, Fibrillogenesis