Gut Inflammation in HLA-B27 Transgenic Rats Alters the Monocyte Compartment and Its Osteoclastogenic Potential

Ansalone, C., Utriainen, L., Milling, S. W.F. and Goodyear, C. S. (2015) Gut Inflammation in HLA-B27 Transgenic Rats Alters the Monocyte Compartment and Its Osteoclastogenic Potential. ACR/ARHP Annual Meeting, San Francisco, CA, USA, 6-11 Nov 2015.

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Background: Human HLA-B27 and β2-microglobulin transgenic rats (B27 rats), an animal model for spondyloarthropathies, spontaneously develop inflammatory colitis and bone loss. We have previously demonstrated that B27 rats lack specific myeloid cell populations but it is not known whether gut inflammation drives systemic symptoms. Here we have examined central and peripheral myeloid cells, focusing on osteoclast precursors. To investigate the link between colitis and the peripheral disease we have assessed the effects of oral antibiotic treatment on intestinal pathology, and the subsequent systemic impacts. Methods: Bone marrow (BM) and blood, from 14-16 week old B27 and control (B7) rats, were evaluated by flow cytometry for expression of CD90, CD3, CD45RA, Igκ, CD172a, CD43, and CD11b, and uptake of fluorescent M-CSF and CCL2. Plasma CCL2 levels were measured by ELISA. Monocytes from BM and blood were FACS sorted and cultured in pro-osteoclastogenic medium to evaluate osteoclastogenic potential. Mature osteoclasts, tartrate-resistant acid phosphatase positive multinucleated cells, were counted. Some B27 rats were given oral antibiotics for 4 weeks. Guts were collected for H&E staining and monocytes were analysed by flow cytometry. BM cells were cultured in pro-osteoclastogenic medium ± TNF-α and the generated osteoclasts were counted. Results: Rat central and peripheral monocytes comprise two main subsets: Lin-(CD90-CD3-CD45RA-Igκ-)CD172a+CD11b+CD43hi and Lin-CD172a+ CD11b+CD43low. A Lin-CD172a+CD43lowCD11blow BM monocyte subset has also been described. In B27 rats, there was a substantial increase in the number of circulating Lin-CD172a+CD43low monocytes, which significantly correlated with higher levels of plasma CCL2. Interestingly, this population of monocytes (in BM and blood) has the greatest in vitro osteoclastogenic potential. Antibiotic treatment of rats substantially reduced colitis, plasma CCL2 levels, and the number of central and circulating Lin-CD172a+CD11b+CD43low monocytes. Finally, antibiotic treatment also prevented the previously described TNF-α enhanced osteoclastogenesis observed in transgenic B27 rats. Conclusions: B27 rats have increased numbers of myeloid osteoclast progenitors in the circulation and bone marrow, and higher levels of the monocyte chemokine CCL2, potentially contributing to enhanced inflammation and bone loss. Importantly, antibiotic treatment not only reduced gut inflammation but also decreased circulating levels of CCL2 and Lin-CD172a+CD11b+CD43low cells. This study therefore provides a link between colitis and systemic inflammation, and a mechanism connecting these with altered bone homeostasis.

Item Type:Conference or Workshop Item
Keywords:Antibiotics, microbiome, monocytes, osteoclastogenesis and spondylarthropathy.
Glasgow Author(s) Enlighten ID:Milling, Professor Simon and Utriainen, Dr Lotta and Ansalone, Dr Cecilia and Goodyear, Professor Carl
Authors: Ansalone, C., Utriainen, L., Milling, S. W.F., and Goodyear, C. S.
Subjects:R Medicine > RB Pathology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Published Online:29 September 2015
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