Can serum biomarker assays measure the progression of cartilage degeneration in osteoarthritis?

Abstract

A loss of homeostasis in the maintenance of a healthy articular cartilage leads to the pathologic degeneration of articular cartilage in osteoarthritis (OA). The preservation of a functional articular cartilage enables the survival of a tissue that covers articulating surfaces in a diarthrodial joint. With synovial fluid, articular cartilage provides an almost frictionless articulation enabling painless joint movement. The extracellular matrix of articular cartilage provides this tissue with its great strength, resistance to deformation, and ability to dissipate load and handle the forces generated within the joint. The collagen fibrillar network provides tensile strength, and the water-laden proteoglycan aggrecan, organized in a supramolecular aggregate, contributes its compressive stiffness. Ordinarily, articular cartilage can easily manage the high pressures, strains, and shear forces generated during running, jumping, stair climbing, and descent (1).In short, articular cartilage is a remarkable tissue and an engineering marvel. Yet this tissue is incapable of effective repair once growth ceases, mainly because of its lack of vascularity and the resulting inability to recruit chondroprogenitor (stem) cells. Its physical properties peak at an age of ϳ30 years and are usually progressively lost thereafter, much less in the ankle than in the hip or knee, but lost nonetheless. As we age, the degenerative process becomes more apparent. In a majority of the population over age 60, this process can result in OA (2). Clearly, our joints were never designed for us to live so long. Long life brings out the weaknesses in the maintenance of our structural design.This degeneration is not simply wear and tear, although the mechanical issues are extremely important. In the mouse bearing the active human collagenase 3 (matrix metalloproteinase 13 [MMP-13]) transgene, cleavage of type II collagen occurs throughout the articular cartilage, but it is only at sites of direct contact of articular cartilage that focal lesions develop (3). It is the combination of molecular damage and inability to effectively manage physical forces that leads to pathology. The latter must also involve altered loading on chondrocytes due to differences and alterations in joint shape and function and matrix degradation, resulting in joint incongruity and attendant macro-and microenvironmental changes in loading, promoting changes in matrix turnover and a loss of homeostasis. The net result is lesion development that we see so often at autopsy. In idiopathic OA, this process is likely to start and progress over the course of Ն20 years before clinical signs and symptoms are recognized.In more intact healthy aging articular cartilages, such as those in the ankle, these overt degradative changes are seen much less often. Here, there are no clear signs of progressive change in the distribution and amount of denatured type II collagen in relationship to the amount of collagenase-cleaved collagen, signs which are indicative of altered proteolysis of this co...

Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury

“…This enigma regarding serum biomarker results has been reported in a human study 19 and has prompted debate regarding the apparent unpredictability of increased or decreased serum biomarker concentrations in response to degenerative changes in joints. 20 It should be noted that changes in serum are reflective of systemic turnover and do not specifically reflect changes that occur in a single joint. Because of hepatic metabolism, the half-lives of biomarkers are much shorter in blood than in synovial fluid, and the magnitude of the difference depends on the biomarker.…”

“…25 Ideally, osteoarthritis biomarkers should be investigated in multiple body fluids (serum, urine, and synovial fluid). 20,21,27 Collection of urine and blood from patients is associated with less complications, compared with synovial fluid. However, synovial fluid should provide the most direct information about changes in the joint.…”

Early changes in serum type ii collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy

“…Cartilage metabolism can be monitored by measurement of the synthesis and the degradation products of cartilagespecific collagens and proteoglycans, which are released into synovial fluid, serum, and urine as byproducts (14). Studies of cartilage turnover using these biomarkers have indicated significant changes that relate to the erosion of articular cartilage in arthritis (15)(16)(17)(18).…”

Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: A three‐month longitudinal study

“…These include magnetic resonance imaging (MRI) (2) and molecular markers of joint tissue turnover (3)(4)(5)(6). Several recent studies have shown that MRI provides accurate and precise evaluation of the key joint structures, including articular cartilage, osteophytes, bone marrow, synovium, ligaments, and menisci, although most of these studies focused on cartilage assessment (7)(8)(9)(10)(11)(12)(13).…”

“…A variety of molecular markers for joint tissue turnover have been described, and these markers differ in terms of their tissue specificity and sensitivity in detecting alterations in OA (3)(4)(5)(6). Among these, urinary excretion of specific fragments of C-terminal crosslinking telopeptide of type II collagen (CTX-II) has been shown to be associated with progression of joint damage in OA (19)(20)(21).…”