Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number235
JournalArthritis Research and Therapy
Volume24
Issue number1
DOIs
Publication statusPublished - 2022 Dec

Keywords

  • Aging
  • Meniscus
  • Mouse models
  • Osteoarthritis
  • Subchondral bone

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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