Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model
Abstract Background Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging. Methods Knees...
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| Language: | English |
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BMC
2022-10-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-022-02916-5 |
| _version_ | 1797986111488786432 |
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| author | Yohei Sanada Yasunari Ikuta Chenyang Ding Masahiro Shinohara Dilimulati Yimiti Hiroyuki Ishitobi Keita Nagira Minjung Lee Takayuki Akimoto Sachi Shibata Masakazu Ishikawa Tomoyuki Nakasa Kiminori Matsubara Martin K. Lotz Nobuo Adachi Shigeru Miyaki |
| author_facet | Yohei Sanada Yasunari Ikuta Chenyang Ding Masahiro Shinohara Dilimulati Yimiti Hiroyuki Ishitobi Keita Nagira Minjung Lee Takayuki Akimoto Sachi Shibata Masakazu Ishikawa Tomoyuki Nakasa Kiminori Matsubara Martin K. Lotz Nobuo Adachi Shigeru Miyaki |
| author_sort | Yohei Sanada |
| collection | DOAJ |
| description | Abstract Background Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging. Methods Knees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as control from 6 to 33 weeks of age were evaluated by histological grading systems for joint tissues (cartilage, meniscus, synovium, and subchondral bone), and µCT analysis. Gene expression patterns in articular cartilage were analyzed by real-time PCR. Immunohistochemistry was performed for OA-related factors, senescence markers, and apoptosis. Results Starting at 14 weeks of age, SAMP8 exhibited mild OA-like changes such as proteoglycan loss and cartilage fibrillation. From 18 to 33 weeks of age, SAMP8 progressed to partial or full-thickness defects with exposure of subchondral bone on the medial tibia and exhibited synovitis. Histological scoring indicated significantly more severe OA in SAMP8 compared with SAMR1 from 14 weeks [median (interquartile range): SAMR1: 0.89 (0.56–1.81) vs SAMP8: 1.78 (1.35–4.62)] to 33 weeks of age [SAMR1: 1.67 (1.61–1.04) vs SAMP8: 13.03 (12.26–13.57)]. Subchondral bone sclerosis in the medial tibia, bone mineral density (BMD) loss of femoral metaphysis, and meniscus degeneration occurred much earlier than the onset of cartilage degeneration in SAMP8 at 14 weeks of age. Conclusions SAMP8 are a spontaneous OA model that is useful for investigating the pathogenesis of primary OA and evaluating therapeutic interventions. |
| first_indexed | 2024-04-11T07:27:45Z |
| format | Article |
| id | doaj.art-858d78eac3ea481294fd92a47106f8d7 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T07:27:45Z |
| publishDate | 2022-10-01 |
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| series | Arthritis Research & Therapy |
| spelling | doaj.art-858d78eac3ea481294fd92a47106f8d72022-12-22T04:37:01ZengBMCArthritis Research & Therapy1478-63622022-10-0124111710.1186/s13075-022-02916-5Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis modelYohei Sanada0Yasunari Ikuta1Chenyang Ding2Masahiro Shinohara3Dilimulati Yimiti4Hiroyuki Ishitobi5Keita Nagira6Minjung Lee7Takayuki Akimoto8Sachi Shibata9Masakazu Ishikawa10Tomoyuki Nakasa11Kiminori Matsubara12Martin K. Lotz13Nobuo Adachi14Shigeru Miyaki15Medical Center for Translational and Clinical Research, Hiroshima University HospitalDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Rehabilitation for the Movement Functions, National Rehabilitation Center for Persons With DisabilitiesDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityMedical Center for Translational and Clinical Research, Hiroshima University HospitalDepartment of Orthopaedic Surgery, Tottori UniversityFaculty of Sport Sciences, Waseda UniversityFaculty of Sport Sciences, Waseda UniversityDepartment of Human Life Science Education, Graduate School of Education, Hiroshima UniversityDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityDepartment of Human Life Science Education, Graduate School of Education, Hiroshima UniversityDepartment of Molecular Medicine, Scripps ResearchDepartment of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima UniversityMedical Center for Translational and Clinical Research, Hiroshima University HospitalAbstract Background Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging. Methods Knees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as control from 6 to 33 weeks of age were evaluated by histological grading systems for joint tissues (cartilage, meniscus, synovium, and subchondral bone), and µCT analysis. Gene expression patterns in articular cartilage were analyzed by real-time PCR. Immunohistochemistry was performed for OA-related factors, senescence markers, and apoptosis. Results Starting at 14 weeks of age, SAMP8 exhibited mild OA-like changes such as proteoglycan loss and cartilage fibrillation. From 18 to 33 weeks of age, SAMP8 progressed to partial or full-thickness defects with exposure of subchondral bone on the medial tibia and exhibited synovitis. Histological scoring indicated significantly more severe OA in SAMP8 compared with SAMR1 from 14 weeks [median (interquartile range): SAMR1: 0.89 (0.56–1.81) vs SAMP8: 1.78 (1.35–4.62)] to 33 weeks of age [SAMR1: 1.67 (1.61–1.04) vs SAMP8: 13.03 (12.26–13.57)]. Subchondral bone sclerosis in the medial tibia, bone mineral density (BMD) loss of femoral metaphysis, and meniscus degeneration occurred much earlier than the onset of cartilage degeneration in SAMP8 at 14 weeks of age. Conclusions SAMP8 are a spontaneous OA model that is useful for investigating the pathogenesis of primary OA and evaluating therapeutic interventions.https://doi.org/10.1186/s13075-022-02916-5OsteoarthritisAgingMouse modelsSubchondral boneMeniscus |
| spellingShingle | Yohei Sanada Yasunari Ikuta Chenyang Ding Masahiro Shinohara Dilimulati Yimiti Hiroyuki Ishitobi Keita Nagira Minjung Lee Takayuki Akimoto Sachi Shibata Masakazu Ishikawa Tomoyuki Nakasa Kiminori Matsubara Martin K. Lotz Nobuo Adachi Shigeru Miyaki Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model Arthritis Research & Therapy Osteoarthritis Aging Mouse models Subchondral bone Meniscus |
| title | Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model |
| title_full | Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model |
| title_fullStr | Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model |
| title_full_unstemmed | Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model |
| title_short | Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model |
| title_sort | senescence accelerated mice prone 8 samp8 in male as a spontaneous osteoarthritis model |
| topic | Osteoarthritis Aging Mouse models Subchondral bone Meniscus |
| url | https://doi.org/10.1186/s13075-022-02916-5 |
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