Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies

El-Zayadi, A.A., Jones, E.A., Churchman, S.M., Baboolal, T.G., Cuthbert, R.J., El-Jawhari, J.J., Badawy, A.M., Alase, A.A., El-Sherbiny, Y.M. ORCID: 0000-0003-4791-3475 and McGonagle, D., 2017. Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology, 56 (3), pp. 488-493. ISSN 1462-0324

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Abstract

Objectives. The Spondyloarthropathies (SpAs) are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesised that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis.

Methods. The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-け and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real time-polymerase chain reaction (qRTPCR) for MSC lineage markers and osteogenesis assays were used.

Results. Combined treatment of MSC with IL-22, IFN-け and TNF resulted in increased MSC proliferation (p=0.008) and migration (p=0.04); an effect which was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic, adipogenic but not chondrogenic transcription factors were up-regulated by IL-22 alone (p<0.05). MSC osteogenesis was enhanced following IL-22 exposure (p=0.03, measured by calcium production). The combination of IFN-け and TNF with or without IL-22, suppressed MSC osteogenesis (p=0.03).

Conclusion. This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments with MSC osteogenesis occurring only in IFN-け/TNF absence. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.

Item Type: Journal article
Publication Title: Rheumatology
Creators: El-Zayadi, A.A., Jones, E.A., Churchman, S.M., Baboolal, T.G., Cuthbert, R.J., El-Jawhari, J.J., Badawy, A.M., Alase, A.A., El-Sherbiny, Y.M. and McGonagle, D.
Publisher: Oxford University Press on behalf of the British Society for Rheumatology
Date: 1 March 2017
Volume: 56
Number: 3
ISSN: 1462-0324
Identifiers:
NumberType
10.1093/rheumatology/kew384DOI
Divisions: Schools > School of Science and Technology
Depositing User: Jill Tomkinson
Date Added: 26 Feb 2019 11:58
Last Modified: 26 Feb 2019 11:58
URI: http://irep.ntu.ac.uk/id/eprint/35785

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