Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra-1 in Mice

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Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra-1 in Mice. / Schwabe, Kay; Garcia, Mireia; Ubieta, Kenia; Hannemann, Nicole; Herbort, Bettina; Luther, Julia; Noël, Daniele; Jorgensen, Christian; Casteilla, Louis; David, Jean-Pierre; Stock, Michael; Herrmann, Martin; Schett, Georg; Bozec, Aline.

In: ARTHRITIS RHEUM-US, Vol. 68, No. 1, 01.2016, p. 138-51.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Schwabe, K, Garcia, M, Ubieta, K, Hannemann, N, Herbort, B, Luther, J, Noël, D, Jorgensen, C, Casteilla, L, David, J-P, Stock, M, Herrmann, M, Schett, G & Bozec, A 2016, 'Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra-1 in Mice', ARTHRITIS RHEUM-US, vol. 68, no. 1, pp. 138-51. https://doi.org/10.1002/art.39425

APA

Schwabe, K., Garcia, M., Ubieta, K., Hannemann, N., Herbort, B., Luther, J., Noël, D., Jorgensen, C., Casteilla, L., David, J-P., Stock, M., Herrmann, M., Schett, G., & Bozec, A. (2016). Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra-1 in Mice. ARTHRITIS RHEUM-US, 68(1), 138-51. https://doi.org/10.1002/art.39425

Vancouver

Bibtex

@article{c43426dff97b4804a1fcaf91aadb9510,
title = "Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra-1 in Mice",
abstract = "OBJECTIVE: To determine whether overexpression of the activator protein 1 (AP-1) transcription factor Fra-1 in adipose-derived stromal cells (ADSCs) is an effective treatment of collagenase-induced osteoarthritis (OA).METHODS: OA was induced by injection of collagenase into the knee joints of male C57BL/6 mice. ADSCs were isolated from the inguinal fat pads of 8-week-old wild-type or Fra-1-transgenic mice and injected into the knee joints of mice with collagenase-induced OA 7 days after OA induction. Histologic analyses of cartilage destruction and chondrocyte cell death were performed. Adipogenic differentiation capacity was evaluated, gene expression was analyzed, and cytokine profiling was performed in stromal vascular fractions (SVFs) and ADSCs.RESULTS: OA-related cartilage destruction and chondrocyte cell death were significantly reduced in mouse knee joints treated with ADSCs from Fra-1-transgenic mice compared to mouse knee joints treated with ADSCs from wild-type mice. This effect did not result from the higher number of adipogenic progenitors observed in SVFs from Fra-1-transgenic compared to wild-type mouse fat pads, since injection of wild-type mouse ADSCs enriched for adipogenic progenitors did not show any additional chondroprotective effects compared to nonsorted ADSCs. However, Fra-1-transgenic mouse ADSCs showed decreased adipogenic differentiation capacity. Moreover, Fra-1 significantly inhibited proinflammatory interleukin-6 and pentraxin 3 expression, while increasing the expression of extracellular matrix proteins, such as periostin and spondin 1. These findings suggest that Fra-1 overexpression leads to an increased chondroprotective effect of ADSCs in OA.CONCLUSION: ADSCs overexpressing Fra-1 effectively protect against OA. Our data indicate that genetic modifications of ADSCs, such as Fra-1 overexpression, may improve their potential to protect articular cartilage against OA-mediated damage.",
author = "Kay Schwabe and Mireia Garcia and Kenia Ubieta and Nicole Hannemann and Bettina Herbort and Julia Luther and Daniele No{\"e}l and Christian Jorgensen and Louis Casteilla and Jean-Pierre David and Michael Stock and Martin Herrmann and Georg Schett and Aline Bozec",
note = "{\textcopyright} 2016, American College of Rheumatology.",
year = "2016",
month = jan,
doi = "10.1002/art.39425",
language = "English",
volume = "68",
pages = "138--51",
journal = "ARTHRITIS RHEUMATOL",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra-1 in Mice

AU - Schwabe, Kay

AU - Garcia, Mireia

AU - Ubieta, Kenia

AU - Hannemann, Nicole

AU - Herbort, Bettina

AU - Luther, Julia

AU - Noël, Daniele

AU - Jorgensen, Christian

AU - Casteilla, Louis

AU - David, Jean-Pierre

AU - Stock, Michael

AU - Herrmann, Martin

AU - Schett, Georg

AU - Bozec, Aline

N1 - © 2016, American College of Rheumatology.

PY - 2016/1

Y1 - 2016/1

N2 - OBJECTIVE: To determine whether overexpression of the activator protein 1 (AP-1) transcription factor Fra-1 in adipose-derived stromal cells (ADSCs) is an effective treatment of collagenase-induced osteoarthritis (OA).METHODS: OA was induced by injection of collagenase into the knee joints of male C57BL/6 mice. ADSCs were isolated from the inguinal fat pads of 8-week-old wild-type or Fra-1-transgenic mice and injected into the knee joints of mice with collagenase-induced OA 7 days after OA induction. Histologic analyses of cartilage destruction and chondrocyte cell death were performed. Adipogenic differentiation capacity was evaluated, gene expression was analyzed, and cytokine profiling was performed in stromal vascular fractions (SVFs) and ADSCs.RESULTS: OA-related cartilage destruction and chondrocyte cell death were significantly reduced in mouse knee joints treated with ADSCs from Fra-1-transgenic mice compared to mouse knee joints treated with ADSCs from wild-type mice. This effect did not result from the higher number of adipogenic progenitors observed in SVFs from Fra-1-transgenic compared to wild-type mouse fat pads, since injection of wild-type mouse ADSCs enriched for adipogenic progenitors did not show any additional chondroprotective effects compared to nonsorted ADSCs. However, Fra-1-transgenic mouse ADSCs showed decreased adipogenic differentiation capacity. Moreover, Fra-1 significantly inhibited proinflammatory interleukin-6 and pentraxin 3 expression, while increasing the expression of extracellular matrix proteins, such as periostin and spondin 1. These findings suggest that Fra-1 overexpression leads to an increased chondroprotective effect of ADSCs in OA.CONCLUSION: ADSCs overexpressing Fra-1 effectively protect against OA. Our data indicate that genetic modifications of ADSCs, such as Fra-1 overexpression, may improve their potential to protect articular cartilage against OA-mediated damage.

AB - OBJECTIVE: To determine whether overexpression of the activator protein 1 (AP-1) transcription factor Fra-1 in adipose-derived stromal cells (ADSCs) is an effective treatment of collagenase-induced osteoarthritis (OA).METHODS: OA was induced by injection of collagenase into the knee joints of male C57BL/6 mice. ADSCs were isolated from the inguinal fat pads of 8-week-old wild-type or Fra-1-transgenic mice and injected into the knee joints of mice with collagenase-induced OA 7 days after OA induction. Histologic analyses of cartilage destruction and chondrocyte cell death were performed. Adipogenic differentiation capacity was evaluated, gene expression was analyzed, and cytokine profiling was performed in stromal vascular fractions (SVFs) and ADSCs.RESULTS: OA-related cartilage destruction and chondrocyte cell death were significantly reduced in mouse knee joints treated with ADSCs from Fra-1-transgenic mice compared to mouse knee joints treated with ADSCs from wild-type mice. This effect did not result from the higher number of adipogenic progenitors observed in SVFs from Fra-1-transgenic compared to wild-type mouse fat pads, since injection of wild-type mouse ADSCs enriched for adipogenic progenitors did not show any additional chondroprotective effects compared to nonsorted ADSCs. However, Fra-1-transgenic mouse ADSCs showed decreased adipogenic differentiation capacity. Moreover, Fra-1 significantly inhibited proinflammatory interleukin-6 and pentraxin 3 expression, while increasing the expression of extracellular matrix proteins, such as periostin and spondin 1. These findings suggest that Fra-1 overexpression leads to an increased chondroprotective effect of ADSCs in OA.CONCLUSION: ADSCs overexpressing Fra-1 effectively protect against OA. Our data indicate that genetic modifications of ADSCs, such as Fra-1 overexpression, may improve their potential to protect articular cartilage against OA-mediated damage.

U2 - 10.1002/art.39425

DO - 10.1002/art.39425

M3 - SCORING: Journal article

C2 - 26361381

VL - 68

SP - 138

EP - 151

JO - ARTHRITIS RHEUMATOL

JF - ARTHRITIS RHEUMATOL

SN - 2326-5191

IS - 1

ER -