The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM)
AbstractOsteoarthritis (OA) is a common debilitating disease primarily characterised by excessive loss of the articular ECM, which is composed of up to 95% type II collagen. Among the factors that contribute to the pathogenesis of OA, the natural process of aging is regarded as the most significant...
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| Format: | Article |
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Taylor & Francis Group
2020-01-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2019.1699802 |
| _version_ | 1797788709083414528 |
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| author | Zhuqing Zha Qingmin Han Shaochuan Huo |
| author_facet | Zhuqing Zha Qingmin Han Shaochuan Huo |
| author_sort | Zhuqing Zha |
| collection | DOAJ |
| description | AbstractOsteoarthritis (OA) is a common debilitating disease primarily characterised by excessive loss of the articular ECM, which is composed of up to 95% type II collagen. Among the factors that contribute to the pathogenesis of OA, the natural process of aging is regarded as the most significant risk factor. AGEs, which are extremely resilient to degradation, are produced in the body naturally as a result of the Maillard process of nonenzymatic glycation and are also introduced through diet and tobacco smoke. AGEs have a high affinity for collagen and therefore accumulate in joint tissues, where they induce increased expression of proinflammatory cytokines, chemokines, and degradative enzymes. Additionally, AGEs induce oxidative stress, which further exacerbates the degradative process. Type II collagen is targeted for degradation by matrix metalloproteinases (MMPs), particularly MMP-3 and MMP-13, and AGEs have been shown to trigger increased expression of these MMPs. The role of retinoid and rexinoid receptors as specific treatment targets has been receiving increasing attention. Bexarotene is a retinoid X receptor (RXR) agonist used for the treatment of T-cell lymphoma and other cancers which has displayed a favourable safety profile. Here, we examined the roles of RXR agonism using bexarotene on AGE-induced markers of OA, including oxidative stress, inflammatory response, and MMP-mediated degradation of type II collagen. Furthermore, we demonstrate that bexarotene inhibited phosphorylation of IκBα, thereby suppressing activation of the proinflammatory NF-κB cellular signalling pathway. These findings present a basis for selective targeting of RXR by bexarotene as a potential treatment of OA induced by AGEs. |
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| institution | Directory Open Access Journal |
| issn | 2169-1401 2169-141X |
| language | English |
| last_indexed | 2024-03-13T01:40:21Z |
| publishDate | 2020-01-01 |
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| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj.art-08cc60e049c141aab61634b8ae8017d52023-07-03T14:04:57ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2020-01-014811710.1080/21691401.2019.1699802The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM)Zhuqing Zha0Qingmin Han1Shaochuan Huo2Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Zhengzhou, Henan, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaShenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, ChinaAbstractOsteoarthritis (OA) is a common debilitating disease primarily characterised by excessive loss of the articular ECM, which is composed of up to 95% type II collagen. Among the factors that contribute to the pathogenesis of OA, the natural process of aging is regarded as the most significant risk factor. AGEs, which are extremely resilient to degradation, are produced in the body naturally as a result of the Maillard process of nonenzymatic glycation and are also introduced through diet and tobacco smoke. AGEs have a high affinity for collagen and therefore accumulate in joint tissues, where they induce increased expression of proinflammatory cytokines, chemokines, and degradative enzymes. Additionally, AGEs induce oxidative stress, which further exacerbates the degradative process. Type II collagen is targeted for degradation by matrix metalloproteinases (MMPs), particularly MMP-3 and MMP-13, and AGEs have been shown to trigger increased expression of these MMPs. The role of retinoid and rexinoid receptors as specific treatment targets has been receiving increasing attention. Bexarotene is a retinoid X receptor (RXR) agonist used for the treatment of T-cell lymphoma and other cancers which has displayed a favourable safety profile. Here, we examined the roles of RXR agonism using bexarotene on AGE-induced markers of OA, including oxidative stress, inflammatory response, and MMP-mediated degradation of type II collagen. Furthermore, we demonstrate that bexarotene inhibited phosphorylation of IκBα, thereby suppressing activation of the proinflammatory NF-κB cellular signalling pathway. These findings present a basis for selective targeting of RXR by bexarotene as a potential treatment of OA induced by AGEs.https://www.tandfonline.com/doi/10.1080/21691401.2019.1699802Bexaroteneretinoid X receptor (RXR)osteoarthritisAGEsoxidative stressmatrix metalloproteinases |
| spellingShingle | Zhuqing Zha Qingmin Han Shaochuan Huo The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM) Artificial Cells, Nanomedicine, and Biotechnology Bexarotene retinoid X receptor (RXR) osteoarthritis AGEs oxidative stress matrix metalloproteinases |
| title | The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM) |
| title_full | The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM) |
| title_fullStr | The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM) |
| title_full_unstemmed | The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM) |
| title_short | The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM) |
| title_sort | protective effects of bexarotene against advanced glycation end product age induced degradation of articular extracellular matrix ecm |
| topic | Bexarotene retinoid X receptor (RXR) osteoarthritis AGEs oxidative stress matrix metalloproteinases |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2019.1699802 |
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