Morphological changes of skeletal muscle, tendon and periosteum in the senescence-accelerated mouse (SAMP6): A murine model 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.
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Materials and methods
SAMP6/Ta and SAMR1/Ta mice were kindly donated by the Council for SAM Research, Kyoto, Japan. Animals were maintained under conventional conditions and had free access to tap water and commercial diet (CE-2, CLEA Japan). All animal experiments were undertaken in accordance with the guidelines for care and use of laboratory animals, Gifu University Graduate School of Medicine. In this study, we used 1-, 2-, 5- and 8-month-old female mice of both SAMP6 and SAMR1 of 8 each totaling 64 animals.
The
Results
In SAMR1, the soleus muscle contained 30.3% type I fiber at 1 month of age. Type I fiber predominance gradually became apparent with advancing age. At 8 months of age, type I fiber increased to 58.6% of the whole. The age distribution of fiber type in SAMP6 was similar to that of SAMR1. For both SAMP6 and SAMR1 strains, the effect of age was significant (Table 1). In SAMP6, the soleus muscle contained 72.4% type I fiber at 8 months of age, much more than that of SAMR1 (Table 1).
The
Discussion
In the present study, the atrophy of muscle fibers and the degenerative changes of muscle–tendon junctions were recognized in SAMP6 at 8 months of age. We also found the regressive changes of the tendon and periosteum in SAMP6 at 5 and 8 months of age. The above results showed morphologically the aging signs of the skeleton muscles and tendon at the early stage in SAMP6. Similar results have been reported in a variety of mammalian species with advancing age.
The atrophy of skeletal muscle and
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