Blood and urinary collagen markers in osteoarthritis: markers of tissue turnover and disease activity

ABSTRACT

Introduction: The need for diagnostic markers in osteoarthritis (OA) is acute and immediate, as sensitive and precise tools that monitor disease activity and treatment response are lacking. Collagens – types I, II, and III – are the skeleton of the extracellular matrix of joint tissues. Joint collagens are generally turned over at a low rate, but the balance between formation and degradation is disturbed, leading to the loss of, for example, cartilage.

Areas covered: We discuss the markers reflecting collagen turnover and provide examples of how they have been applied in OA research, as well as how we believe these should be used in the future. We have searched PubMed for full-text articles written in English using different combinations of the following terms: OA, biomarker, and collagen. The result is a narrative review that gives examples from the literature.

Expert opinion: Collagen markers show promise, as they are direct measures of tissue balance. Until now, collagen markers have mainly been tested in observational cohorts, which may provide insights into the association between the candidate marker and clinical variables; however, these do not advance the development of qualified markers that can be used for drug development or in clinical practice.

KEYWORDS:

• Osteoarthritis
• cartilage
• synovium
• biochemical marker
• collagens

Article highlights

• There is a need to understand the biomarkers that can be used in OA. This knowledge can help in the development and application of biomarkers in OA research and drug development.

• The main collagens of the joint are types I (bone and connective tissue), II (cartilage), and III (the synovium, ligaments), but other collagens are also present in the joint, such as types VI, IX, X, and XI.

• The regulation of collagenous tissues is altered in OA; types I and III collagen expressions are increased as a part of subchondral and synovial thickening, respectively. Type X collagen expression is activated as a part of chondrocyte hypertrophy, whereas type II collagen is mainly lost because of excessive degradation.

• Markers measuring the formation and degradation fragments of collagens in the blood or urine reflect changes in tissue turnover.

Acknowledgments

We would like to acknowledge our research teams at Nordic Bioscience for moral and scientific input.

Declaration of interest

Anne Christine Bay-Jensen is a member of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) Consortium, a 5-year project funded by the European Commission’s Innovative Medicines Initiative (IMI). APPROACH is a public-private partnership directed towards osteoarthritis biomarker development through the establishment of a heavily phenotyped and comprehensively analyzed longitudinal cohort. The research leading to these results has received partial support from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115770, resources of which are composed of financial contribution from the European Union’s Seventh Framework programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. ACBJ and MK are full-time employees and shareholder at Nordic Bioscience, a privately-owned biotech company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

A reviewer on this manuscript has disclosed being a founder and president of Artialis SA. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript did not receive any direct funding, but is considered sideground under the Innovative medicine initiative (IMI) funded project called APPROACH (grant no.: 115770).