Mass Spectrometry-based Biomarkers for Knee Osteoarthritis: A Systematic Review

ABSTRACT

Introduction

Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to the finding of this ‘OA biomarker’ is mass spectrometry (MS), which offers the possibility to analyze different molecules in tissues or fluids. Several proteomic, lipidomic, metabolomic and other – omic approaches aim to identify these molecular profiles; however, variation in methods and techniques complicate the finding of promising candidate biomarkers.

Areas covered

In this systematic review, we aim to provide an overview of molecules in knee OA patients. Possible biomarkers in several tissue types of OA and non-OA patients, as well as current limitations and possible future suggestions will be discussed.

Expert opinion

According to this review, we do not believe one specific biomarker will function as predictive molecule for OA. Likely, a group of molecules will give insight in OA development and possible therapeutic targets. For clinical implementation of MS-analysis in clinical decision-making, standardized procedures, large cohort studies and sharing protocols and data is necessary.

KEYWORDS:

• Biomarker
• hoffa’s fat pad
• infrapatellar fat pad
• lipidomics
• mass spectrometry
• metabolomics
• osteoarthritis
• proteomics
• total knee arthroplasty
• total knee replacement

Supplemental Material

Supplemental data for this article can be accessed here

Article highlights

• Mass spectrometry (imaging) is a promising tool for the detection (and can provide spatial information) of biomarkers for osteoarthritis.

• In the literature, synovial fluid is found to be the preferred source in the search for biomarkers for osteoarthritis when analyzing proteins, lipids or metabolites.

• A biomarker profile for osteoarthritis is likely to consist of multiple molecules detected in multiple tissues of the effected joint, rather than one specific molecule.

• Current studies on biomarkers for osteoarthritis are built on small sample size, a variety of protocols and databases.

• Clinical implementation can only be accomplished when studies have been conducted on large patient cohorts, with standardized methods and shared data.

List of abbreviations

1H NMR1H; nuclear magnetic resonance spectroscopy

2DE2D; gel electrophoresis

ACL;anterior cruciate ligament

APC;Iatmospheric pressure chemical ionization

APPI;atmospheric pressure photoionization

CI;chemical ionization

COMP;cartilage oligomeric matrix protein

DESI;desorption electrospray ionization

DMOAD;disease modifying osteoarthritis drug

ECM;extracellular matrix

EI;electron ionization

eOA;early osteoarthritis

ESI;electrospray ionization

FDR;false discovery rate

GC-MS;gas chromatography mass spectrometry

HFPH;offa’s fat pad

HPLC-MS;high performance liquid chromatography mass spectrometry

KLK;ellgren-Lawrence

LC-MS (/MS);liquid chromatography (tandem) mass spectrometry

lOA;late osteoarthritis

MALDI;matrix-assisted laser desorption/ionization

MRI;magnetic resonance imaging

MS;mass spectrometry

MSI;mass spectrometry imaging

NSAID;non-steroidal anti-inflammatory drug

OA;osteoarthritis

OPLS-DA;orthogonal partial least squares discriminant analysis

PCA;principal component analysis

SDS-PAGE;sodium dodecyl sulfate polyacrylamide gel electrophoresis

SIMS;secondary ion mass spectrometry

TKA;total knee arthroplasty

TOF;time of flight

Acknowledgments

Figure 1, 3 and 4 were modified from Servier Medical Art, licensed under a Creative Common Attribution 3.0 Generic License. http://smart.servier.com/.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by the Dutch Research Council or “Nederlandse Organisatie voor Wetenschappelijk Onderzoek„ (NWO) domain Applied and Engineering Sciences (P15-23). The funders had no input in study design, data collection or data analysis, and manuscript preparation.