Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage

The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. Secretomes from wild-type and Adam15−/− chondrocytes were compared by label-free quantitative mass spectro...

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Published in:	Osteoarthritis and cartilage open Vol. 2; no. 4; p. 100128
Main Authors:	Yang, C.Y., Chanalaris, A., Bonelli, S., McClurg, O., Hiles, G. Lorenzatti, Cates, A.L., Zarebska, J. Miotla, Vincent, T.L., Day, M.L., Müller, S.A., Lichtenthaler, S.F., Nagase, H., Scilabra, S.D., Troeberg, L.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-12-2020 Elsevier
Subjects:	ADAM15 Age IL-13 Metalloprotease Metalloproteinase Osteoarthritis Metalloprotease Metalloproteinase IL-13 ADAM15 Osteoarthritis Age
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Summary:	The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. Secretomes from wild-type and Adam15−/− chondrocytes were compared by label-free quantitative mass spectrometry. mRNA was isolated from murine knee joints, either with or without surgical induction of osteoarthritis on male C57BL/6 mice, and the expression of Adam15 and other related genes quantified by RT-qPCR. ADAM15 in human normal and osteoarthritic cartilage was investigated similarly and by fluorescent immunohistochemistry. Cultured HTB94 chondrosarcoma cells were treated with various anabolic and catabolic stimuli, and ADAM15 mRNA and protein levels evaluated. There were no significant differences in the secretomes of chondrocytes from WT and Adam15−/− cartilage. Expression of ADAM15 was not altered in either human or murine osteoarthritic cartilage relative to disease-free controls. However, expression of ADAM15 was markedly reduced upon aging in both species, to the extent that expression in joints of 18-month-old mice was 45-fold lower than in that 4.5-month-old animals. IL-13 increased expression of ADAM15 in HTB94 cells by 2.5-fold, while modulators of senescence and autophagy pathways had no effect. Expression of Il13 in the joint was reduced with aging, suggesting this cytokine may control ADAM15 levels in the joint. Expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging human and murine joints, possibly due to a concomitant reduction in IL-13 expression. We thus propose IL-13 as a novel factor contributing to increased osteoarthritis risk upon aging.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Kromek Group plc, NETPark, Thomas Wright Way, Sedgefield, County Durham, TS21 3FD, UK.
ISSN:	2665-9131 2665-9131
DOI:	10.1016/j.ocarto.2020.100128