Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study
The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transecti...
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/6/1209 |
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| author | Prabhakar Busa Sing-Ong Lee Niancih Huang Yaswanth Kuthati Chih-Shung Wong |
| author_facet | Prabhakar Busa Sing-Ong Lee Niancih Huang Yaswanth Kuthati Chih-Shung Wong |
| author_sort | Prabhakar Busa |
| collection | DOAJ |
| description | The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1β to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP’s) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP’s expression levels. When tested using the 2′,7′-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5′,6,6′-tetracholoro-1,1′,3,3′-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study’s investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo. |
| first_indexed | 2024-03-10T00:33:33Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:33:33Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-8d52ddd4717d479796ea8217869dc3982023-11-23T15:21:27ZengMDPI AGAntioxidants2076-39212022-06-01116120910.3390/antiox11061209Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro StudyPrabhakar Busa0Sing-Ong Lee1Niancih Huang2Yaswanth Kuthati3Chih-Shung Wong4Department of Anesthesiology, Cathay General Hospital, Taipei City 106, TaiwanDepartment of Anesthesiology, Cathay General Hospital, Taipei City 106, TaiwanDepartment of Anesthesiology, Tri-Service General Hospital, Taipei City 114, TaiwanDepartment of Anesthesiology, Cathay General Hospital, Taipei City 106, TaiwanDepartment of Anesthesiology, Cathay General Hospital, Taipei City 106, TaiwanThe most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1β to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP’s) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP’s expression levels. When tested using the 2′,7′-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5′,6,6′-tetracholoro-1,1′,3,3′-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study’s investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo.https://www.mdpi.com/2076-3921/11/6/1209knee osteoarthritiscarnosineinterleukin-1βreactive oxygen speciesnuclear factor erythroid 2-related factorheme oxygenase |
| spellingShingle | Prabhakar Busa Sing-Ong Lee Niancih Huang Yaswanth Kuthati Chih-Shung Wong Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study Antioxidants knee osteoarthritis carnosine interleukin-1β reactive oxygen species nuclear factor erythroid 2-related factor heme oxygenase |
| title | Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study |
| title_full | Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study |
| title_fullStr | Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study |
| title_full_unstemmed | Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study |
| title_short | Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study |
| title_sort | carnosine alleviates knee osteoarthritis and promotes synoviocyte protection via activating the nrf2 ho 1 signaling pathway an in vivo and in vitro study |
| topic | knee osteoarthritis carnosine interleukin-1β reactive oxygen species nuclear factor erythroid 2-related factor heme oxygenase |
| url | https://www.mdpi.com/2076-3921/11/6/1209 |
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