Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis

Nat Commun. 2018 Nov 5;9(1):4613. doi: 10.1038/s41467-018-06933-4.


Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation of CCL2 or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Arthritis / diagnostic imaging
  • Arthritis / genetics
  • Arthritis / metabolism*
  • Arthritis / pathology*
  • Autoantibodies / metabolism
  • Autoimmunity
  • Bone Resorption / metabolism
  • Chemokine CXCL1 / metabolism
  • Chemokine CXCL2 / metabolism
  • Chemokines / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Humans
  • Inflammation / metabolism*
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Monocytes
  • Osteoclasts / metabolism
  • Receptors, CCR2 / drug effects
  • Stromal Cells
  • Tarsal Bones / diagnostic imaging
  • Tarsal Bones / pathology
  • Tendinopathy / pathology
  • Tendons / metabolism
  • X-Ray Microtomography


  • Autoantibodies
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines
  • Cxcl1 protein, mouse
  • Cxcl2 protein, mouse
  • Receptors, CCR2