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Semin Immunopathol. 2019 Sep;41(5):583-594. doi: 10.1007/s00281-019-00762-3. Epub 2019 Oct 14.

An emerging role for Toll-like receptors at the neuroimmune interface in osteoarthritis.

Author information

1
Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, 1611 W Harrison Street, Chicago, IL, 60612, USA.
2
Section of Rheumatology and Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz Veterans Affairs Medical Center & Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
3
Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, 1611 W Harrison Street, Chicago, IL, 60612, USA. anne-marie_malfait@rush.edu.

Abstract

Osteoarthritis (OA) is a chronic progressive, painful disease of synovial joints, characterized by cartilage degradation, subchondral bone remodeling, osteophyte formation, and synovitis. It is now widely appreciated that the innate immune system, and in particular Toll-like receptors (TLRs), contributes to pathological changes in OA joint tissues. Furthermore, it is now also increasingly recognized that TLR signaling plays a key role in initiating and maintaining pain. Here, we reviewed the literature of the past 5 years with a focus on how TLRs may contribute to joint damage and pain in OA. We discuss biological effects of specific damage-associated molecular patterns (DAMPs) which act as TLR ligands in vitro, including direct effects on pain-sensing neurons. We then discuss the phenotype of transgenic mice that target TLR pathways, and provide evidence for a complex balance between pro- and anti-inflammatory signaling pathways activated by OA DAMPs. Finally, we summarize clinical evidence implicating TLRs in OA pathogenesis, including polymorphisms and surrogate markers of disease activity. Our review of the literature led us to propose a model where multi-directional crosstalk between connective tissue cells (chondrocytes, fibroblasts), innate immune cells, and sensory neurons in the affected joint may promote OA pathology and pain.

KEYWORDS:

Alarmins; DAMPs; Innate immunity; Osteoarthritis; Pain; TLR

PMID:
31612243
PMCID:
PMC6858588
[Available on 2020-10-14]
DOI:
10.1007/s00281-019-00762-3

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