Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes
Osteoarthritis (OA) is a chronic debilitating joint disease, characterized by degeneration of the cartilage and loss of the cartilage matrix, and it is clinically manifested as joint pain. Osteopontin (OPN) is a glycoprotein that is abnormally expressed in the bone and cartilage tissues and plays a...
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KeAi Communications Co., Ltd.
2023-07-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304222002318 |
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| author | Wei Luo Zili Lin Yuhao Yuan Ziyi Wu Wei Zhong Qing Liu |
| author_facet | Wei Luo Zili Lin Yuhao Yuan Ziyi Wu Wei Zhong Qing Liu |
| author_sort | Wei Luo |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a chronic debilitating joint disease, characterized by degeneration of the cartilage and loss of the cartilage matrix, and it is clinically manifested as joint pain. Osteopontin (OPN) is a glycoprotein that is abnormally expressed in the bone and cartilage tissues and plays a vital role in various pathological processes such as the osteoarthritic inflammatory response and endochondral ossification. The focus of our study is to investigate the therapeutic potential and specific role of OPN in OA. Using morphological comparisons, we found that the cartilage was severely worn-out and there was a significant loss of the cartilage matrix in OA. OPN, CD44, and hyaluronic acid (HA) synthase 1 (HAS1) were highly expressed, and the anabolism of HA was significantly higher in the OA chondrocytes than in the control chondrocytes. Additionally, we treated the OA chondrocytes with small interfering RNA (siRNA) targeting OPN, recombinant human OPN (rhOPN), and a combination of rhOPN and anti-CD44 antibodies. Furthermore, in vivo experiments were performed in mice. We found that OPN upregulated the expression of downstream HAS1 and increased the anabolism of HA through CD44 protein expression in OA mice compared with those in control mice. Moreover, intra-articular injection of OPN in mice with OA significantly inhibited OA progression. In summary, OPN initiates an intracellular cascade via CD44 which results in an anabolic increase in HA levels, thereby inhibiting OA progression. Therefore, OPN is a promising therapeutic agent in precision treatment of OA. |
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| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-13T05:02:20Z |
| publishDate | 2023-07-01 |
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| series | Genes and Diseases |
| spelling | doaj.art-fd567a06765c488dbbb96a3ee84f59592023-06-17T05:19:01ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-07-0110417141725Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytesWei Luo0Zili Lin1Yuhao Yuan2Ziyi Wu3Wei Zhong4Qing Liu5Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China; Corresponding author. Department of Orthopaedics, Xiangya Hospital, Central South University, 87th Xiangya Road, Changsha, Hunan 410008, China.Osteoarthritis (OA) is a chronic debilitating joint disease, characterized by degeneration of the cartilage and loss of the cartilage matrix, and it is clinically manifested as joint pain. Osteopontin (OPN) is a glycoprotein that is abnormally expressed in the bone and cartilage tissues and plays a vital role in various pathological processes such as the osteoarthritic inflammatory response and endochondral ossification. The focus of our study is to investigate the therapeutic potential and specific role of OPN in OA. Using morphological comparisons, we found that the cartilage was severely worn-out and there was a significant loss of the cartilage matrix in OA. OPN, CD44, and hyaluronic acid (HA) synthase 1 (HAS1) were highly expressed, and the anabolism of HA was significantly higher in the OA chondrocytes than in the control chondrocytes. Additionally, we treated the OA chondrocytes with small interfering RNA (siRNA) targeting OPN, recombinant human OPN (rhOPN), and a combination of rhOPN and anti-CD44 antibodies. Furthermore, in vivo experiments were performed in mice. We found that OPN upregulated the expression of downstream HAS1 and increased the anabolism of HA through CD44 protein expression in OA mice compared with those in control mice. Moreover, intra-articular injection of OPN in mice with OA significantly inhibited OA progression. In summary, OPN initiates an intracellular cascade via CD44 which results in an anabolic increase in HA levels, thereby inhibiting OA progression. Therefore, OPN is a promising therapeutic agent in precision treatment of OA.http://www.sciencedirect.com/science/article/pii/S2352304222002318Cartilage degenerationCD44Hyaluronic acidOsteoarthritisOsteopontin |
| spellingShingle | Wei Luo Zili Lin Yuhao Yuan Ziyi Wu Wei Zhong Qing Liu Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes Genes and Diseases Cartilage degeneration CD44 Hyaluronic acid Osteoarthritis Osteopontin |
| title | Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes |
| title_full | Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes |
| title_fullStr | Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes |
| title_full_unstemmed | Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes |
| title_short | Osteopontin (OPN) alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes |
| title_sort | osteopontin opn alleviates the progression of osteoarthritis by promoting the anabolism of chondrocytes |
| topic | Cartilage degeneration CD44 Hyaluronic acid Osteoarthritis Osteopontin |
| url | http://www.sciencedirect.com/science/article/pii/S2352304222002318 |
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