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  • Review Article
  • Published:

Why location matters — site-specific factors in rheumatic diseases

Nature Reviews Rheumatology volume 13, pages 433–442 (2017)Cite this article

Subjects

Key Points

  • Site-specific pathognomonic disease patterns are based on three interconnected mechanisms, namely site-specific local cells, systemic factors that affect particular anatomical sites and local mechanical factors

  • Synovial fibroblasts and chondrocytes differ substantially between joints and might create location-specific joint microenvironments, rendering each joint more or less susceptible to different types of arthritis

  • Evidence is emerging that local differences in joint innervation and vasculature might influence arthritis patterns; however, further studies are needed to strengthen these observations

  • Local mechanical factors can aggravate joint disease, yet whether they trigger disease locally needs further clarification

  • The overlap between site-specific embryonic traits and disease location suggests a role for embryonic pathways in the pathogenesis and occurrence of disease in joints, as well as in other organs

Abstract

Rheumatic diseases follow a characteristic anatomical pattern of joint and organ involvement. This Review explores three interconnected mechanisms that might be involved in the predilection of specific joints for developing specific forms of arthritis: site-specific local cell types that drive disease; systemic triggers that affect local cell types; and site-specific exogenous factors, such as focal mechanical stress, that activate cells locally. The embryonic development of limbs and joints is also relevant to the propensity of certain joints to develop arthritis. Additionally, location-specific homeostasis and disease occurs in skin and blood vessels, thereby extending the concept of site-specificity in human diseases beyond rheumatology. Acknowledging the importance of site-specific parameters increases the complexity of current disease paradigms and brings us closer to understanding why particular disease processes manifest at a particular location.

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Figure 1: Patterns of joint and organ involvement in rheumatic disease.
Figure 2: Anatomical diversity in joints and patterns of joint involvement in rheumatic disease.
Figure 3: Development of limbs and digits in vertebrates.
Figure 4: Morphogenesis of synovial joints.

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Acknowledgements

The authors would like to thank M. Trenkmann for assistance in editing this Review.

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  1. Centre of Experimental Rheumatology, University Hospital Zurich, Wagistrasse 14, Schlieren, CH-8952, Zurich, Switzerland

    Caroline Ospelt & Mojca Frank-Bertoncelj

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Both authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to Caroline Ospelt.

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Ospelt, C., Frank-Bertoncelj, M. Why location matters — site-specific factors in rheumatic diseases. Nat Rev Rheumatol 13, 433–442 (2017). https://doi.org/10.1038/nrrheum.2017.96

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