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El-Zayadi, AA, Jones, EA, Churchman, SM, Baboolal, TG, Cuthbert, RJ, El-Jawhari, JJ, Badawy, AM, Alase, AA, El-Sherbiny, YM 
ORCID: https://orcid.org/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: | Number Type 10.1093/rheumatology/kew384 DOI |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Jill Tomkinson |
| Date Added: | 26 Feb 2019 11:58 |
| Last Modified: | 26 Feb 2019 11:58 |
| URI: | https://irep.ntu.ac.uk/id/eprint/35785 |
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