Title

Associations Between Extracellular Matrix Proteins in the Pericellular Environment of Bovine Cartilage Tissue: Interaction of Collagen α1(XI) and Thrombospondin-1

Publication Date

12-2011

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Biology

Department

Biology

Major Advisor

Julia Thom Oxford, Ph.D.

Abstract

Millions of people worldwide are affected each year with debilitating – and in some cases life-threatening – skeletal disorders. Primarily caused by a malfunction or degeneration of cartilage tissue; affected individuals display a wide range of symptoms and disease characteristics from severe craniofacial deformities to the painful loss of joint cushioning cartilage. The organization of the collagen fibers that make up this tissue is essential to the function of cartilage. At the heart of many of these diseases is the loss of integrity and viability of cartilage tissue. Osteoarthritis is a degenerative disease resulting in a painful loss of joint mobility caused by loss of cartilage between bones in articulating joints. Early onset osteoarthritis has been attributed to the disorganization of the collagen fibrils, which is caused by a mutation in the Collagen α1(XI) gene (COL11A1).

Collagen type XI is a heterotypic, quantitatively minor component of the cartilage extracellular matrix. A heterotrimer composed of three alpha chains: α1, α2, and α3, collagen type XI has previously been shown to play a vital role in the organization and regulation of cartilage fibril diameter through association with the major component of cartilage – collagen type II. The amino terminal domain of collagen type XI is localized on the surface of the collagen fibrils where it regulates fibril growth and organization.

The research described here was carried out to elucidate the exact mechanisms through which collagen type XI regulates fibril diameter and cartilage tissue integrity. Many studies have attributed the function of collagen type XI to steric hindrance; however, this may be an incomplete explanation. An initial literature review identified several candidate proteins for association, including Cartilage Oligomeric Matrix Protein (COMP), Cartilage Matrix Protein (CMP), and Thrombospondin 1 (TSP-1). Results presented here identify an association between the extracellular matrix molecule TSP-1 and the amino terminal domain of collagen type XI on the surface of collagen fibrils. An interaction between collagen type XI and Thrombospondin-1 may play a role in the regulation of cartilage fibril diameter. These interactions are also predicted to affect the organization of the cartilage extracellular matrix and could have serious implications for the structural integrity of resulting cartilage and bone. Results from this research contribute to the understanding of the role collagen type XI in collagen and cartilage related diseases. Understanding how these molecules interact may provide opportunities for drug targeting or therapy for patients with cartilage and bone dysplasias.

Comments

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