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.
Objectives.
The 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 hypothesize 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-γ and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used.


Results.
Combined treatment of MSC with IL-22, IFN-γ and TNF resulted in increased MSC proliferation ( P = 0.008) and migration ( P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated 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-γ 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 the absence of IFN-γ/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.
['El-Zayadi|Ahmed A|AA|', 'Jones|Elena A|EA|', 'Churchman|Sarah M|SM|', 'Baboolal|Thomas G|TG|', 'Cuthbert|Richard J|RJ|', 'El-Jawhari|Jehan J|JJ|', 'Badawy|Ahmed M|AM|', 'Alase|Adewonuola A|AA|', 'El-Sherbiny|Yasser M|YM|', 'McGonagle|Dennis|D|']
D050156:Adipogenesis D002454:Cell Differentiation D002465:Cell Movement D049109:Cell Proliferation D002478:Cells, Cultured D020219:Chondrogenesis D016207:Cytokines D005434:Flow Cytometry D006801:Humans D007371:Interferon-gamma D007378:Interleukins D059630:Mesenchymal Stem Cells D010012:Osteogenesis D060888:Real-Time Polymerase Chain Reaction D018123:Receptors, Interleukin D025242:Spondylarthropathies D014157:Transcription Factors D014409:Tumor Necrosis Factor-alpha D015854:Up-Regulation
mesenchymal stem cells spondyloarthropathy IL-22 osteogenesis IL-23 axis