Morphological changes of skeletal muscle, tendon and periosteum in the senescence-accelerated mouse (SAMP6): A murine model for senile osteoporosis

Abstract

SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. Previously we observed age-related changes of the bone in SAMP6. In the present study, we investigated the morphology of the skeletal muscle, tendon and periosteum in SAMP6 and age-matched normal mouse SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 and 2 months of age. As compared with SAMR1, the cross-sectional area of type I and type II muscle fibers of the soleus muscle were significantly low in SAMP6 at 8 months of age. The projections in the interface of the muscle–tendon junctions were significantly decreased in SAMP6 at 8 months of age. The number of fibroblasts and the diameter of the tendon collagen fibers in Achilles fiber were significantly reduced in SAMP6 at 8 months of age. The diameter of Sharpey's fiber reduced in SAMP6 at 5 and 8 months of age. Some chondrocytes in the insertions of Achilles tendon and some osteogenic cells in the periosteum showed degenerative changes in SAMP6 at 5 and 8 months of age. The pronounced degenerative changes were detected in the skeletal muscle, muscle–tendon junction, tendon, tendon–bone interface and periosteum in SAMP6 with age. These findings indicated the atrophy of skeletal muscle, degeneration of tendon and periosteum in SAMP6, which may be involved in the bone loss for senile osteoporosis.

Introduction

Osteoporosis is becoming a major public health problem in all developed countries. A progressive loss of bone mass and subsequent structural weakness are physiological phenomena associated with age. There is little information on age-related changes of bone in experimental animals. Senescence-accelerated mouse P6 (SAMP6) was reported to be the first spontaneous mouse model for senile osteoporosis (Takeda et al., 1981). SAMP6 exhibited a significant decrease on bone mineral density (BMD) and bone formation early in life when compared with normal mouse SAMR1 (Kawase et al., 1989). Recently, we found that the bone mass was significantly reduced, the number of osteoblasts and the percentage area of the bone forming surfaces in the femoral endosteal surface decreased in SAMP6 as early as at 2 months of age. We consider that the reduction of osteoblast bone formation involves in the bone loss in SAMP6 (Chen et al., 2004). Silva et al. (2005) reported that the periosteal bone formation was unimpaired in SAMP6, but there has been no information about the periosteal morphology of SAMP6 and SAMR1.

Bone metabolism is affected by skeletal muscle, tendon and periosteum. It is generally recognized that muscle traction determines bone mass. Reduced muscular function will result in osteoporosis. Muscles are attached to bone by tendons composed of collagen fibers, which are embedded into bone as Sharpey's fibers. Tendons transfer muscular forces to the bone surface and reduced muscular activity adversely affects the structure of the tendon and the strength of its attachment to bone. Skeletal muscles deteriorate functionally in old age. It was demonstrated that a reduced mean fiber diameter in many muscles in human subjects older than 40 years (Moore et al., 1971). With increasing age, type II fibers selectively decreased, while type I fiber predominance was apparent (Poggi et al., 1987). In rabbit Achilles tendons, the number of fibroblasts decreased and the diameter of collagen fibers declined for 4–5-year-old than those for 8–10-month-old (Nakagawa et al., 1994). It seems that the size of collagen fibers and fibroblasts might affect the physiological functions associated with aging. It was observed that the reduction of periosteal cells and the thinning of periosteum with age, which may explain why periosteal bone formation decline in older subjects (Allen et al., 2004). However, few data are available concerning the ultrastructural aspect of the skeletal muscle, tendon and periosteum in SAMP6. The purpose of the present study was to investigate the changes of muscle fiber size and fiber type distribution, tendon fibroblasts and collagen fibers and periosteal cells concomitant with age in SAMP6 and SAMR1 to determine the properties which account for the bone loss in senile osteoporotic animals.