Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes

Osteoarthritis (OA) most frequently affects the knee joint and is associated with an elevated expression of cytokines and extracellular cartilage matrix (ECM), degrading enzymes such as matrix metalloproteinases (MMPs). Differences in gene expression of the intra-articularly located infrapatellar fa...

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Main Authors: Ewa Wisniewska, Dominik Laue, Jacob Spinnen, Leonard Kuhrt, Benjamin Kohl, Patricia Bußmann, Carola Meier, Gundula Schulze-Tanzil, Wolfgang Ertel, Michal Jagielski
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/24/2850
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author Ewa Wisniewska
Dominik Laue
Jacob Spinnen
Leonard Kuhrt
Benjamin Kohl
Patricia Bußmann
Carola Meier
Gundula Schulze-Tanzil
Wolfgang Ertel
Michal Jagielski
author_facet Ewa Wisniewska
Dominik Laue
Jacob Spinnen
Leonard Kuhrt
Benjamin Kohl
Patricia Bußmann
Carola Meier
Gundula Schulze-Tanzil
Wolfgang Ertel
Michal Jagielski
author_sort Ewa Wisniewska
collection DOAJ
description Osteoarthritis (OA) most frequently affects the knee joint and is associated with an elevated expression of cytokines and extracellular cartilage matrix (ECM), degrading enzymes such as matrix metalloproteinases (MMPs). Differences in gene expression of the intra-articularly located infrapatellar fat pad (IPFP) and other fatty tissue suggest its autonomous function, yet its role in OA pathogenesis remains unknown. Human IPFPs and articular cartilage were collected from OA patients undergoing total knee arthroplasty, and biopsies from the IPFP of healthy patients harvested during knee arthroscopy served as controls (CO). Isolated chondrocytes were co-cultured with either osteoarthritic (OA) or CO-IPFPs in a transwell system. Chondrocyte expression of <i>MMP1</i>, -<i>3</i>, -<i>13</i>, <i>type 1</i> and <i>2 collagens</i>, <i>interleukin IL1β</i>, <i>IL6</i>, <i>IL10</i>, and <i>tumor necrosis factor TNFα</i> was analyzed by RTD-PCR at day 0 and day 2, and TNFα secretion was analyzed by ELISA. The cytokine release in IPFPs was assessed by an array. Results: Both IPFPs (CO, OA) significantly reduced the expression of <i>type 2 collagen</i> and <i>TNFα</i> in chondrocytes. On the other hand, only CO-IPFP suppressed the expression of <i>type 1 collagen</i> and significantly induced the <i>MMP13</i> expression. On the contrary, <i>IL1β</i> and <i>IL6</i> were significantly induced when exposed to OA-IPFP. Conclusions: The partial loss of the suppressive effect on <i>type 1 collagen</i> gene expression found for OA-IPFP shows the pathological remodeling and dedifferentiation potential of the OA-IPFP on the chondrocytes. However, the significant suppression of <i>TNFα</i> implies that the OA- and CO-IPFP could also exhibit a protective role in the knee joint, preventing the progress of inflammation.
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spelling doaj.art-0577b15e6d0a4188ab9205d56ed7345e2023-12-22T13:59:47ZengMDPI AGCells2073-44092023-12-011224285010.3390/cells12242850Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular ChondrocytesEwa Wisniewska0Dominik Laue1Jacob Spinnen2Leonard Kuhrt3Benjamin Kohl4Patricia Bußmann5Carola Meier6Gundula Schulze-Tanzil7Wolfgang Ertel8Michal Jagielski9Department of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyInstitute of Anatomy and Cell Biology, Paracelsus Medical University (PMU), Prof.-Ernst Nathan Strasse 1, 90419 Nuremberg, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of Traumatology and Reconstructive Surgery, Campus Benjamin Franklin, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Hindenburgdamm 30, 12203 Berlin, GermanyOsteoarthritis (OA) most frequently affects the knee joint and is associated with an elevated expression of cytokines and extracellular cartilage matrix (ECM), degrading enzymes such as matrix metalloproteinases (MMPs). Differences in gene expression of the intra-articularly located infrapatellar fat pad (IPFP) and other fatty tissue suggest its autonomous function, yet its role in OA pathogenesis remains unknown. Human IPFPs and articular cartilage were collected from OA patients undergoing total knee arthroplasty, and biopsies from the IPFP of healthy patients harvested during knee arthroscopy served as controls (CO). Isolated chondrocytes were co-cultured with either osteoarthritic (OA) or CO-IPFPs in a transwell system. Chondrocyte expression of <i>MMP1</i>, -<i>3</i>, -<i>13</i>, <i>type 1</i> and <i>2 collagens</i>, <i>interleukin IL1β</i>, <i>IL6</i>, <i>IL10</i>, and <i>tumor necrosis factor TNFα</i> was analyzed by RTD-PCR at day 0 and day 2, and TNFα secretion was analyzed by ELISA. The cytokine release in IPFPs was assessed by an array. Results: Both IPFPs (CO, OA) significantly reduced the expression of <i>type 2 collagen</i> and <i>TNFα</i> in chondrocytes. On the other hand, only CO-IPFP suppressed the expression of <i>type 1 collagen</i> and significantly induced the <i>MMP13</i> expression. On the contrary, <i>IL1β</i> and <i>IL6</i> were significantly induced when exposed to OA-IPFP. Conclusions: The partial loss of the suppressive effect on <i>type 1 collagen</i> gene expression found for OA-IPFP shows the pathological remodeling and dedifferentiation potential of the OA-IPFP on the chondrocytes. However, the significant suppression of <i>TNFα</i> implies that the OA- and CO-IPFP could also exhibit a protective role in the knee joint, preventing the progress of inflammation.https://www.mdpi.com/2073-4409/12/24/2850IPFPOAosteoarthritiscartilagechondrocytesMMPs
spellingShingle Ewa Wisniewska
Dominik Laue
Jacob Spinnen
Leonard Kuhrt
Benjamin Kohl
Patricia Bußmann
Carola Meier
Gundula Schulze-Tanzil
Wolfgang Ertel
Michal Jagielski
Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes
Cells
IPFP
OA
osteoarthritis
cartilage
chondrocytes
MMPs
title Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes
title_full Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes
title_fullStr Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes
title_full_unstemmed Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes
title_short Infrapatellar Fat Pad Modulates Osteoarthritis-Associated Cytokine and MMP Expression in Human Articular Chondrocytes
title_sort infrapatellar fat pad modulates osteoarthritis associated cytokine and mmp expression in human articular chondrocytes
topic IPFP
OA
osteoarthritis
cartilage
chondrocytes
MMPs
url https://www.mdpi.com/2073-4409/12/24/2850
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