RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling
Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was perfo...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Orthopaedic Translation |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X24000056 |
| _version_ | 1797202119501021184 |
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| author | Jinjian Zhu Liangliang Liu Rengui Lin Xiongtian Guo Jianbin Yin Haoyu Xie Yuheng Lu Zhicheng Zhang Hongbo Zhang Zihao Yao Haiyan Zhang Xiangjiang Wang Chun Zeng Daozhang Cai |
| author_facet | Jinjian Zhu Liangliang Liu Rengui Lin Xiongtian Guo Jianbin Yin Haoyu Xie Yuheng Lu Zhicheng Zhang Hongbo Zhang Zihao Yao Haiyan Zhang Xiangjiang Wang Chun Zeng Daozhang Cai |
| author_sort | Jinjian Zhu |
| collection | DOAJ |
| description | Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy. |
| first_indexed | 2024-04-24T07:58:22Z |
| format | Article |
| id | doaj.art-879bfbfbb6824d2490ca5504c34f0b1b |
| institution | Directory Open Access Journal |
| issn | 2214-031X |
| language | English |
| last_indexed | 2024-04-24T07:58:22Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj.art-879bfbfbb6824d2490ca5504c34f0b1b2024-04-18T04:20:26ZengElsevierJournal of Orthopaedic Translation2214-031X2024-03-0145226235RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signalingJinjian Zhu0Liangliang Liu1Rengui Lin2Xiongtian Guo3Jianbin Yin4Haoyu Xie5Yuheng Lu6Zhicheng Zhang7Hongbo Zhang8Zihao Yao9Haiyan Zhang10Xiangjiang Wang11Chun Zeng12Daozhang Cai13Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaDepartment of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, ChinaOrthopedics department, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, 511518, Guangdong, China; Corresponding author.Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China; Corresponding author. Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, China.Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Disease, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510280, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China; Corresponding author. Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, China.Objectives: To investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model. Methods: RNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes. Results: The protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway. Conclusions: These findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment. The translational potential of this article: It is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.http://www.sciencedirect.com/science/article/pii/S2214031X24000056ChondrocyteHedgehog pathwayOsteoarthritisRibosomal protein L35Senescence |
| spellingShingle | Jinjian Zhu Liangliang Liu Rengui Lin Xiongtian Guo Jianbin Yin Haoyu Xie Yuheng Lu Zhicheng Zhang Hongbo Zhang Zihao Yao Haiyan Zhang Xiangjiang Wang Chun Zeng Daozhang Cai RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling Journal of Orthopaedic Translation Chondrocyte Hedgehog pathway Osteoarthritis Ribosomal protein L35 Senescence |
| title | RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling |
| title_full | RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling |
| title_fullStr | RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling |
| title_full_unstemmed | RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling |
| title_short | RPL35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via Hedgehog-Gli1 signaling |
| title_sort | rpl35 downregulated by mechanical overloading promotes chondrocyte senescence and osteoarthritis development via hedgehog gli1 signaling |
| topic | Chondrocyte Hedgehog pathway Osteoarthritis Ribosomal protein L35 Senescence |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X24000056 |
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