TY - JOUR
T1 - IL-17 inhibits chondrogenic differentiation of human mesenchymal stem cells
AU - Kondo, Masahiro
AU - Yamaoka, Kunihiro
AU - Sonomoto, Koshiro
AU - Fukuyo, Shunsuke
AU - Oshita, Koichi
AU - Okada, Yosuke
AU - Tanaka, Yoshiya
N1 - Funding Information:
Yoshiya Tanaka has read the journal’s policy and has the following conflicts: YT received consulting fees, lecture fees, and/or honoraria from Mitsubishi-Tanabe Pharma, Eisai, Chugai Pharma, Abbott Japan, Astellas Pharma, Daiichi-Sankyo, Abbvie, Janssen Pharma, Pfizer, Takeda Pharma, Astra-Zeneca, Eli Lilly Japan, GlaxoSmithKline, Quintiles, MSD, Asahi-Kasei Pharma, and received research grants from Bristol-Myers, Mitsubishi-Tanabe Pharma, Abbvie, MSD, Chugai Pharma, Astellas Pharma, Daiichi-Sankyo. MK and KO are employees of the Mitsubishi Tanabe Pharma Corporation. KY received consulting fees from Pfizer. The authors declare that there has been no significant financial support for this work which could have influenced its outcome, and this does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2013/11/15
Y1 - 2013/11/15
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0079463
DO - 10.1371/journal.pone.0079463
M3 - Article
C2 - 24260226
AN - SCOPUS:84896704152
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 11
M1 - e79463
ER -