Biomarkers and proteomic analysis of osteoarthritis

Abstract

Our friend and colleague, Dr. Dick Heinegård, contributed greatly to the understanding of joint tissue biochemistry, the discovery and validation of arthritis-related biomarkers and the establishment of methodology for proteomic studies in osteoarthritis (OA). To date, discovery of OA-related biomarkers has focused on cartilage, synovial fluid and serum. Methods, such as affinity depletion and hyaluronidase treatment have facilitated proteomics discovery research from these sources. Osteoarthritis usually involves multiple joints; this characteristic makes it easier to detect OA with a systemic biomarker but makes it hard to delineate abnormalities of individual affected joints. Although the abundance of cartilage proteins in urine may generally be lower than other tissue/sample sources, the protein composition of urine is much less complex and its collection is non-invasive thereby facilitating the development of patient friendly biomarkers. To date however, relatively few proteomics studies have been conducted in OA urine. Proteomics strategies have identified many proteins that may relate to pathological mechanisms of OA. Further targeted approaches to validate the role of these proteins in OA are needed. Herein we summarize recent proteomic studies related to joint tissues and the cohorts used; a clear understanding of the cohorts is important for this work as we expect that the decisive discoveries of OA-related biomarkers rely on comprehensive phenotyping of healthy non-OA and OA subjects. Besides the common phenotyping criteria that include, gender, age, and body mass index (BMI), it is essential to collect data on symptoms and signs of OA outside the index joints and to bolster this with objective imaging data whenever possible to gain the most precise appreciation of the total burden of disease. Proteomic studies on systemic biospecimens, such as serum and urine, rely on comprehensive phenotyping data to unravel the true meaning of the proteomic results.

Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use

“…Proteomics methods have identified many proteins that may relate to pathological mechanisms of OA (for review see [25]). For instance, the OA synovial fluid proteome implicates proteins related to formation and remodeling of the extracellular matrix [26], and the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway [27].…”

A current view of perlecan in physiology and pathology: A mosaic of functions

“…An example of proteoglycan versatility comes in the form of perlecan, an immense heparan sulfate proteoglycan primarily localized to basement membranes and pericellular spaces [4–9]. The modular structure of perlecan enables homeostatic regulation within a vast array of cellular processes including cell adhesion [10,11], endocytosis [12], bone and cartilage formation [13–16], lipid metabolism [17], peripheral node assembly [18], inflammation and wound healing [19,20], thrombosis [21], cancer angiogenesis [9,11,22–33], cardiovascular development [34], and autophagy [35,36]. Given the gargantuan structure and multitude of functions of perlecan, it is no surprise that its gene, HSPG2 , is similarly large and transcriptionally controlled by complex promoter interactions.…”

Comprehensive Metaproteomic Analyses of Urine in the Presence and Absence of Neutrophil-Associated Inflammation in the Urinary Tract

“…For example, a peptidomics study identified three urinary fibrinogen peptides as biomarkers for necrotizing enterocolitis, a leading cause of morbidity and mortality in premature infants 13. Similarly, shotgun proteomics has been used in biomarker studies for renal and urinary tract diseases14 and disease conditions, not in anatomical proximity to the site of sample collection, such as cancer,15 aging,16 osteoarthritis,17 and preeclampsia 18. Urine has also been pre-fractionated to characterize subsets of its proteome, which include exosomes and microparticles.…”