WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice
The anabolic effects of WNT16 on osteoblasts are well established, however, little is known regarding the role of WNT16 in chondrocytes. In this study, we evaluated <i>Wnt16</i> expression and its biological effects on mouse articular chondrocytes (ACs), since these cells are key to the...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/4/878 |
| _version_ | 1827744613332418560 |
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| author | Subburaman Mohan Shelia Pourteymoor Chandrasekhar Kesavan |
| author_facet | Subburaman Mohan Shelia Pourteymoor Chandrasekhar Kesavan |
| author_sort | Subburaman Mohan |
| collection | DOAJ |
| description | The anabolic effects of WNT16 on osteoblasts are well established, however, little is known regarding the role of WNT16 in chondrocytes. In this study, we evaluated <i>Wnt16</i> expression and its biological effects on mouse articular chondrocytes (ACs), since these cells are key to the development of osteoarthritis. While ACs derived from the long bone epiphysis of 7-day old C57BL/6J mice express multiple <i>Wnt</i>s, <i>Wnt5b and Wnt16</i> represent the two most highly expressed <i>Wnt</i>s (expressed at several-fold higher levels than other <i>Wnt</i>s). Treatment of serum-free AC cultures, with 100 ng/mL of recombinant human (rh) WNT16 for 24 h (hrs), increased proliferation (20%, <i>p</i> < 0.05) and expression levels of makers (<i>Sox9 and Col2</i>) of immature chondrocytes at both 24 h and 72 h, while <i>Acan</i> increased at 72 h. Expression of <i>Mmp9</i>, a marker of mature chondrocytes was decreased at 24 h. Additionally, WNT16 treatment regulated expression levels of <i>Wnt</i> ligands in a biphasic manner, inhibiting its expression at 24 h, while stimulating expression at 72 h. To determine whether WNT16 exerted anabolic effects on the AC phenotype, ex vivo cultures of tibial epiphyses were treated with rhWNT16 or vehicle for 9 days, and the articular cartilage phenotype was evaluated by safranin O cartilage staining and expression of articular cartilage marker genes. Both articular cartilage area and expression levels of AC markers were increased after rhWNT16 treatment. Our data suggest that Wnt16 expressed in ACs may play a role in regulating joint cartilage homeostasis via its direct effect, as well as through modulating the expression of other <i>Wnt</i> ligands. |
| first_indexed | 2024-03-11T04:49:41Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T04:49:41Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | Life |
| spelling | doaj.art-0e80de92f8954b9b800d434967b085b92023-11-17T20:04:53ZengMDPI AGLife2075-17292023-03-0113487810.3390/life13040878WNT16 Regulation of the Articular Chondrocyte Phenotype in MiceSubburaman Mohan0Shelia Pourteymoor1Chandrasekhar Kesavan2Musculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAMusculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAMusculoskeletal Disease Center, VA Loma Linda Healthcare System, Loma Linda, CA 92357, USAThe anabolic effects of WNT16 on osteoblasts are well established, however, little is known regarding the role of WNT16 in chondrocytes. In this study, we evaluated <i>Wnt16</i> expression and its biological effects on mouse articular chondrocytes (ACs), since these cells are key to the development of osteoarthritis. While ACs derived from the long bone epiphysis of 7-day old C57BL/6J mice express multiple <i>Wnt</i>s, <i>Wnt5b and Wnt16</i> represent the two most highly expressed <i>Wnt</i>s (expressed at several-fold higher levels than other <i>Wnt</i>s). Treatment of serum-free AC cultures, with 100 ng/mL of recombinant human (rh) WNT16 for 24 h (hrs), increased proliferation (20%, <i>p</i> < 0.05) and expression levels of makers (<i>Sox9 and Col2</i>) of immature chondrocytes at both 24 h and 72 h, while <i>Acan</i> increased at 72 h. Expression of <i>Mmp9</i>, a marker of mature chondrocytes was decreased at 24 h. Additionally, WNT16 treatment regulated expression levels of <i>Wnt</i> ligands in a biphasic manner, inhibiting its expression at 24 h, while stimulating expression at 72 h. To determine whether WNT16 exerted anabolic effects on the AC phenotype, ex vivo cultures of tibial epiphyses were treated with rhWNT16 or vehicle for 9 days, and the articular cartilage phenotype was evaluated by safranin O cartilage staining and expression of articular cartilage marker genes. Both articular cartilage area and expression levels of AC markers were increased after rhWNT16 treatment. Our data suggest that Wnt16 expressed in ACs may play a role in regulating joint cartilage homeostasis via its direct effect, as well as through modulating the expression of other <i>Wnt</i> ligands.https://www.mdpi.com/2075-1729/13/4/878WNT16osteoarthritischondrocytesmicechondrogenesiscell culture |
| spellingShingle | Subburaman Mohan Shelia Pourteymoor Chandrasekhar Kesavan WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice Life WNT16 osteoarthritis chondrocytes mice chondrogenesis cell culture |
| title | WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice |
| title_full | WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice |
| title_fullStr | WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice |
| title_full_unstemmed | WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice |
| title_short | WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice |
| title_sort | wnt16 regulation of the articular chondrocyte phenotype in mice |
| topic | WNT16 osteoarthritis chondrocytes mice chondrogenesis cell culture |
| url | https://www.mdpi.com/2075-1729/13/4/878 |
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