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 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.

Expression of calcitonin gene‐related peptide induces ligament degeneration through endochondral ossification in osteoarthritis

“…45 In the report detailing OA changes in SAMP8, 4 weeks of age showed no OA change in the knee joint, but a roughened articular cartilage surface, fibrillation, and proteoglycan loss in the articular cartilage started at 11 weeks of age and the severity of OA increased over time. 46 As the natural course of OA progression in SAMP8 mice is quite similar to that in humans, SAMP8 mice are useful for investigating the pathogenesis of primary OA. Second, human ACL-derived cells were used in in vitro studies although in vivo studies focused on the PCL.…”

“…Moreover, SAMP8, which has been established as a spontaneous OA model, was used to evaluate the time course of ligament degeneration in OA progression 45 . In the report detailing OA changes in SAMP8, 4 weeks of age showed no OA change in the knee joint, but a roughened articular cartilage surface, fibrillation, and proteoglycan loss in the articular cartilage started at 11 weeks of age and the severity of OA increased over time 46 . As the natural course of OA progression in SAMP8 mice is quite similar to that in humans, SAMP8 mice are useful for investigating the pathogenesis of primary OA.…”

Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis

“…In line with a previous report, all mice were housed in groups of three to five per cage (S 143 mm × 293 mm × H 148 mm) with sterilized beta-chip bedding and maintained at 23 ± 1 °C with a 12-h light/dark cycle and acidified water and complete commercial pelleted food ad libitum 17 .…”

“…As a spontaneous age-related OA model, senescence-accelerated mice (SAM)-prone 8 (SAMP8) (4-week- old male; n = 48) were used 17 – 19 . Mice were obtained from Japan SLC (Shizuoka, Japan).…”

“…To evaluate the effect of rimegepant before and after subchondral bone sclerosis, two groups were set up, one administered starting at 4 weeks of age before the subchondral bone sclerosis occurs and the other at 13 weeks of age when the subchondral bone sclerosis had already occurred according to the previous report (each group: 4 weeks of age, n = 12; 13 weeks of age, n = 12) (Supplementary Fig. 1 ) 17 , 20 . Rimegepant or PBS was administered weekly intraperitoneally, and the group injected at 4 weeks was euthanized at 9 weeks, and the group injected at 13 weeks was euthanized at 23 weeks by an anaesthetic overdose of isoflurane, and tissues were harvested.…”