Chapter 62Markers of Osteoarthritis

Implications for Early Diagnosis and Monitoring of the Pathological Course and Effects of Therapy

Although joint disease can be diagnosed using routine clinical methods, more accurate and earlier diagnosis may lead to identification of osteoarthritis (OA) before irreversible changes occur within joint tissues. Measuring levels of molecular products of tissue turnover, known as biomarkers, from healthy and diseased cartilage and bone has the potential to achieve early diagnosis and allow a better understanding of the pathophysiology of OA. The potential also exists to monitor disease, especially in response to novel therapeutic agents. Work with biomarkers of articular cartilage and bone in people and horses with OA has yielded promising results. This chapter discusses some of the markers that currently are being evaluated in synovial fluid and serum samples, with a focus on those of potential benefit to the equine industry.

Structure and Metabolism of Articular Cartilage and Bone in Health and Disease

Articular cartilage is a complex tissue with an extensive extracellular matrix. The two main components that define the cartilage matrix are type II collagen and aggrecan (see Chapter 61). A balance of synthesis and degradation orchestrated by the chondrocytes maintains normal populations of these molecules within the cartilage matrix. Osteocytes, osteoblasts, and osteoclasts maintain the structural and functional integrity of bone matrix by regulating synthetic and degradative pathways. Synoviocytes also influence homeostasis in cartilage and bone. OA often is characterized by degradative changes within articular cartilage, bone, and synovium. Direct and indirect factors assault the matrix molecules of these tissues, resulting in degeneration and loss of some macromolecules.

What are direct and indirect molecular markers? Direct molecular markers specifically identify a known molecular process within a given tissue. For example, fibrillar collagens, such as types I and II, are synthesized as immature procollagens that undergo proteolytic changes before conversion to mature collagen fibrils. Peptides at either end of the procollagen molecule are cleaved before the procollagen is incorporated into a mature collagen fibril. Estimations of type II collagen synthesis were obtained from synovial fluid and serum samples by using a specific antibody that recognizes the propeptides cleaved from the carboxyl termini.¹ Conversely, an indirect molecular marker reflects more general change that is not clearly definable and may represent contributions from several events and tissues. Indirect markers are cytokines, growth factors, and matrix metalloproteinases (MMPs). OA involves changes in subchondral bone and synovium; therefore assessment of molecular markers from these tissues is relevant.