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Innate Immune Responses and Osteoarthritis

  • Osteoarthritis (M Goldring, Section Editor)
  • Published:
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Abstract

Purpose of the Review

Osteoarthritis (OA) is a chronic, painful joint disease that affects approximately 40% of adults over 70 year. Age is the strongest predictor of OA, while obesity is considered the primary preventable risk factor for OA. Both conditions are associated with abnormal innate immune inflammatory responses that contribute to OA progression and are the focus of this review.

Recent Findings

Recent studies have identified risk factors for OA progression including increased innate immune responses secondary to aging-associated myeloid skewing, obesity-related myeloid activation, and synovial tissue hyperplasia with activated macrophage infiltration. Toll-like receptor (TLR)4-induced catabolic responses also play a significant role in OA.

Summary

The complex interplay between obesity and aging-associated macrophage activation, pro-inflammatory cytokine production from TLR-driven responses, and adipokines leads to a vicious cycle of synovial hyperplasia, macrophage activation, cartilage catabolism, infrapatellar fat pad fibrosis, and joint destruction.

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Abbreviations

OA:

Osteoarthritis

DMOADs:

Disease-modifying anti-osteoarthritis drugs

TLR:

Toll-like receptor

IL:

Interleukin

TNF-α:

Tumor necrosis factor-alpha

LPS:

Lipopolysaccharide

IFP:

Infrapatellar fat pad

PGE2:

Prostaglandin E2

BMI:

Body mass index

MMPs:

Metalloproteinases

DMM:

Destabilized medial meniscus

HFD:

High-fat diet

CIs:

Confidence intervals

ceMRI:

Contrast-enhanced MRI

US:

Ultrasound

SPECT-CT:

Single-photon emission computed tomography

Nf-ĸB:

Nuclear factor kappa-light-chain enhancer of activated B cells

iNOS:

Nitric oxide synthase

COX-2:

Cyclooxygenase-2

CCL:

Chemokine (C-C motif) ligand

CXCL:

C-X-C motif chemokine ligand

IL-1Ra:

Interleukin 1 receptor antagonist

IP-10:

Interferon-gamma-inducible protein

MCP-1:

Monocyte chemotactic protein-1

DAMPS:

Danger-associated molecular patterns

HMGB1:

Hyaluronan and high-mobility group box chromosomal protein

FFA:

Free fatty acids

SDF1:

Stromal-derived-factor-1

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Acknowledgements

The authors are supported by VA PECASE Award (MBH), Presbyterian Health Foundation Bridge Award (MBH), NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R03AR066828 and National Institute on Aging grant R01AG049058) (TMG), and Children’s Hospital Foundation Award (EK).

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Authors and Affiliations

  1. University of Kentucky Barnstable Brown Diabetes Center, University of Kentucky College of Medicine, Lexington, KY, 40536, USA

    Evangelia Kalaitzoglou

  2. Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA

    Timothy M. Griffin

  3. University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Mary Beth Humphrey

  4. Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA

    Mary Beth Humphrey

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  1. Evangelia Kalaitzoglou
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  2. Timothy M. Griffin
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All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.

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Correspondence to Mary Beth Humphrey.

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E. Kalaitzoglou, T.M. Griffin, and M.B. Humphrey declare that they have no conflict of interest.

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This article is part of the Topical Collection on Osteoarthritis

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Kalaitzoglou, E., Griffin, T.M. & Humphrey, M.B. Innate Immune Responses and Osteoarthritis. Curr Rheumatol Rep 19, 45 (2017). https://doi.org/10.1007/s11926-017-0672-6

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