Development of tendon structure and function: regulation of collagen fibrillogenesis.

TLDR

Tendon mechanical properties arise as fibroblast‑produced extracellular matrix—comprising collagen fibrils, fibers, and associated proteins—is assembled and regulated through multiple, independent steps of fibrillogenesis during growth. Collagen fibrillogenesis proceeds through extracellular compartments where immature fibril intermediates fuse into mature fibrils that grow linearly and laterally within fibers, with each step regulated by interactions among minor collagens, fibril‑associated collagens, proteoglycans, and fibroblast‑mediated microdomains.

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.