Seminars in Immunopathology

, Volume 37, Issue 4, pp 407–412 | Cite as

New discoveries in CRMO: IL-1β, the neutrophil, and the microbiome implicated in disease pathogenesis in Pstpip2-deficient mice

  • Polly J. FergusonEmail author
  • Ronald M. Laxer


Chronic non-bacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome are autoinflammatory disorder(s) in which sterile osteomyelitis is frequently accompanied by inflammatory conditions of the joints, skin, or intestine. Patients with CRMO commonly have a personal or family history of psoriasis, inflammatory bowel disease, and inflammatory arthritis, suggesting shared disease pathogenesis. Work by our group and others has demonstrated that dysregulation of interleukin-1 (IL-1) signaling can drive sterile osteomyelitis in the two human monogenic forms of the disease. Recent work in the chronic multifocal osteomyelitis (cmo) mouse model demonstrates that the disease is IL-1-mediated, that neutrophils are critical effector cells and that both caspase-1 and caspase-8 play redundant roles in mediating the cleavage of pro-IL-1β into its biologically active form. Recent data in the cmo mouse demonstrate that dietary manipulation alters the cmo microbiome and can prevent the development of osteomyelitis. Further investigation is needed to determine the specific components of the diet that result in protection from disease and if this finding can be translated into a treatment for human CRMO.


Chronic recurrent multifocal osteomyelitis Pstpip2 Chronic non-bacterial osteomyelitis Autoinflammatory Interleukin-1 beta 



PJF is supported by the National Institutes of Health Grant R01 AR059703.


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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of Iowa Carver College of MedicineIowa CityUSA
  2. 2.Division of RheumatologyThe Hospital for Sick Children and the University of TorontoTorontoCanada

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