The Establishment of a Mouse Model for Degenerative Kyphoscoliosis Based on Senescence-Accelerated Mouse Prone 8

Abstract

Objective: Degenerative kyphoscoliosis (DKS) is a complex spinal deformity associated with degeneration of bones, muscles, discs, and facet joints. The aim of this study was to establish an animal model of degenerative scoliosis that recapitulates key pathological features of DKS and to validate the degenerative changes in senescence-accelerated mouse prone 8 (SAMP8) mice.

Methods: Thirty male mice were divided into 2 groups: 10 bipedal C57BL/6J mice were used as the control group, and 20 bipedal SAMP8 mice were used as the experimental group. Mice were bipedalized under general anesthesia. The incidence of scoliosis and bone quality was determined using radiographs and in vivo micro-CT images 4, 8, and 12 weeks after surgery, respectively. Histomorphological studies of muscle samples were performed after sacrifice at 12 weeks after surgery.

Results: On the 12th week, the incidence rates of kyphosis in C57BL/6J and SAMP8 groups were 50% and 100%, respectively. Overall, the incidence and angle of kyphosis were significantly higher in the bipedal SAMP8 group compared to the C57BL/6J group (44.7°± 6.2° vs. 84.3°± 10.3°, P<0.001). Based on 3D reconstruction of the entire spine, degeneration of the intervertebral disc was observed in bipedal SAMP8 mice, including the reduction of disc height and the formation of vertebral osteophytes. The bone volume ratio (BV/TV) was significantly suppressed in the bipedal SAMP8 group compared with the bipedal C57BL/6J group. In addition, HE staining and Mason staining of the paraspinal muscle tissue showed chronic inflammation and fibrosis in the muscles of the bipedal SAMP8 group.

Conclusions: The SAMP8 mouse model can be taken as a clinically relevant model of DKS, and accelerated aging of the musculoskeletal system promotes the development of kyphosis.

Figure 1

The schematic diagrams of experimental designs.

Figure 2

X-ray and micro-CT assessment of spinal deformities in SAMP8 mice. (a) X-ray examination of mouse spine morphology and calculation of mouse Cobb angle. ^∗P < 0.001, n = 10/group. (b, c) Micro-CT was used to assess trabecular bone microstructure in mice by 3D imaging and to measure the bone volume ratio (BV/TV). ^∗P < 0.001, n = 8/group.

Figure 3

Histological changes in SAMP8 mice. (a) HE staining to examine chronic adipose proliferation in mouse paraspinal muscle tissue. (b) Masson staining to measure collagen fibers and muscle fibers in paraspinal muscle tissue in mice. Scale = 50 μm.