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Review
. 2019 Dec 12:8:F1000 Faculty Rev-2091.
doi: 10.12688/f1000research.20575.1. eCollection 2019.

Recent advances in understanding the phenotypes of osteoarthritis

Ali Mobasheri  1   2   3   4 , Simo Saarakkala  2 , Mikko Finnilä  2 , Morten A Karsdal  4 , Anne-Christine Bay-Jensen  4 , Willem Evert van Spil  5   6
Affiliations
Review

Recent advances in understanding the phenotypes of osteoarthritis

Ali Mobasheri et al. F1000Res. .

Abstract

Recent research in the field of osteoarthritis (OA) has focused on understanding the underlying molecular and clinical phenotypes of the disease. This narrative review article focuses on recent advances in our understanding of the phenotypes of OA and proposes that the disease represents a diversity of clinical phenotypes that are underpinned by a number of molecular mechanisms, which may be shared by several phenotypes and targeted more specifically for therapeutic purposes. The clinical phenotypes of OA supposedly have different underlying etiologies and pathogenic pathways and they progress at different rates. Large OA population cohorts consist of a majority of patients whose disease progresses slowly and a minority of individuals whose disease may progress faster. The ability to identify the people with relatively rapidly progressing OA can transform clinical trials and enhance their efficiency. The identification, characterization, and classification of molecular phenotypes of rapidly progressing OA, which represent patients who may benefit most from intervention, could potentially serve as the basis for precision medicine for this disabling condition. Imaging and biochemical markers (biomarkers) are important diagnostic and research tools that can assist with this challenge.

Keywords: biomarker; clinical phenotype; clinical trials; drug development; imaging; molecular endotype; osteoarthritis; patient stratification.

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Conflict of interest statement

Competing interests: Anne-Christine Bay-Jensen and Morten A. Karsdal are full-time employees and shareholders of Nordic Bioscience, a small–medium enterprise involved in biomarker identification, validation, and development. Ali Mobasheri has consulted for the following companies in the last three years: Abbvie, Aché Laboratórios Farmacêuticos S.A., AlphaSights, Galapagos, Guidepoint Global, Kolon TissueGene, Pfizer Consumer Health (PCH), Servier, Bioiberica S.A. and Science Branding Communications. No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Clinical phenotypes of knee osteoarthritis.
Clinical phenotypes of knee osteoarthritis, as originally identified by Dell’Isola et al. .
Figure 2.
Figure 2.. Summary of the major structural and molecular alterations in osteoarthritis.
Molecular alterations in the micro-environment of chondrocytes and changes in the structure of the extracellular matrix (ECM) alter the behavior and physiology of chondrocytes. ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; MMPs, matrix metalloproteinases; NO, nitric oxide; PGE 2, prostaglandin E2; RAGE, receptor for advanced glycation end-product; ROS, reactive oxygen species; TLR, Toll-like receptor.
Figure 3.
Figure 3.. Senescence-associated secretory phenotype (SASP) in chondrocytes from osteoarthritis cartilage, highlighting phenotypic alterations at the cellular level in cells , .
BMP, bone morphogenetic protein; DAMP, damage-associated molecular pattern; IGF-1, insulin-like growth factor-1; NF-κB, nuclear factor κB; NO, nitric oxide; RAGE, receptor for advanced glycation end-product; ROS, reactive oxygen species; TGF-β, transforming growth factor-β; TLR, Toll-like receptor.
Figure 4.
Figure 4.. Diverse clinical osteoarthritis phenotypes.
Figure 5.
Figure 5.. Venn diagram illustrating diverse overlapping molecular endotypes of osteoarthritis.
Venn diagram illustrating diverse overlapping molecular endotypes of osteoarthritis (OA).
See this image and copyright information in PMC

References

    1. Hunter DJ, Bierma-Zeinstra S: Osteoarthritis. Lancet. 2019;393(10182):1745–59. 10.1016/S0140-6736(19)30417-9 - DOI - PubMed

    2. F1000 Recommendation

    1. Cross M, Smith E, Hoy D, et al. : The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–30. 10.1136/annrheumdis-2013-204763 - DOI - PubMed

    2. F1000 Recommendation

    1. https://www.who.int/medicines/areas/priority_medicines/Ch6_12Osteo.pdf
    1. Lieberthal J, Sambamurthy N, Scanzello CR: Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1825–34. 10.1016/j.joca.2015.08.015 - DOI - PMC - PubMed
    1. Loeser RF, Goldring SR, Scanzello CR, et al. : Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697–707. 10.1002/art.34453 - DOI - PMC - PubMed

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