IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells

Masahiro Kondo, Kunihiro Yamaoka, Koshiro Sonomoto, Shunsuke Fukuyo, Koichi Oshita, Yosuke Okada, Yoshiya Tanaka

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objective: Mesenchymal stem cells (MSCs) can differentiate into cells of mesenchymal lineages, such as osteoblasts and chondrocytes. Here we investigated the effects of IL-17, a key cytokine in chronic inflammation, on chondrogenic differentiation of human MSCs. Methods: Human bone marrow MSCs were pellet cultured in chondrogenic induction medium containing TGF-b3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression. Results: Over-expression of cartilage matrix and chondrogenic marker genes was noted in chondrogenic cultures, but was inhibited by IL-17 in a dose-dependent manner. Expression and phosphorylation of SOX9, the master transcription factor for chondrogenesis, were induced within 2 days and phosphorylated SOX9 was stably maintained until day 21. IL-17 did not alter total SOX9 expression, but significantly suppressed SOX9 phosphorylation in a dose-dependent manner. At day 7, IL-17 also suppressed the activity of cAMP-dependent protein kinase A (PKA), which is known to phosphorylate SOX9. H89, a selective PKA inhibitor, also suppressed SOX9 phosphorylation, expression of chondrogenic markers and cartilage matrix, and also decreased chondrogenesis. Conclusions: IL-17 inhibited chondrogenesis of human MSCs through the suppression of PKA activity and SOX9 phosphorylation. These results suggest that chondrogenic differentiation of MSCs can be inhibited by a mechanism triggered by IL-17 under chronic inflammation.

Original languageEnglish
Article numbere79463
JournalPLoS One
Volume8
Issue number11
DOIs
Publication statusPublished - 2013 Nov 15
Externally publishedYes

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Interleukin-17
Stem cells
Mesenchymal Stromal Cells
cAMP-dependent protein kinase
stem cells
chondrogenesis
Phosphorylation
Cyclic AMP-Dependent Protein Kinases
phosphorylation
Chondrogenesis
cartilage
Cartilage
inflammation
SOX9 Transcription Factor
genetic markers
osteoblasts
chondrocytes
Inflammation
bone marrow cells
dosage

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kondo, M., Yamaoka, K., Sonomoto, K., Fukuyo, S., Oshita, K., Okada, Y., & Tanaka, Y. (2013). IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. PLoS One, 8(11), [e79463]. https://doi.org/10.1371/journal.pone.0079463

IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. / Kondo, Masahiro; Yamaoka, Kunihiro; Sonomoto, Koshiro; Fukuyo, Shunsuke; Oshita, Koichi; Okada, Yosuke; Tanaka, Yoshiya.

In: PLoS One, Vol. 8, No. 11, e79463, 15.11.2013.

Research output: Contribution to journalArticle

Kondo, M, Yamaoka, K, Sonomoto, K, Fukuyo, S, Oshita, K, Okada, Y & Tanaka, Y 2013, 'IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells', PLoS One, vol. 8, no. 11, e79463. https://doi.org/10.1371/journal.pone.0079463
Kondo M, Yamaoka K, Sonomoto K, Fukuyo S, Oshita K, Okada Y et al. IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. PLoS One. 2013 Nov 15;8(11). e79463. https://doi.org/10.1371/journal.pone.0079463
Kondo, Masahiro ; Yamaoka, Kunihiro ; Sonomoto, Koshiro ; Fukuyo, Shunsuke ; Oshita, Koichi ; Okada, Yosuke ; Tanaka, Yoshiya. / IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells. In: PLoS One. 2013 ; Vol. 8, No. 11.
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