|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1994 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1993 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1992 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Disuse atrophy of musculo-skeletal system among aged people, is becoming a serious problem in many developed countries. It is thus mandatory to clarify the mechanism involved in the development of disuse atrophy and to invent countermeasures. Therefore, we investigated the mechanism involved in the disuse atrophy of hindlimb muscles and bones using the tail-suspension model in rats.
I) Studies using grwoing (5-8 week old) rats
Unloading of hindlimbs by tail-suspension for 1-2 weeks resulted in the remarkable atrophy of antigravity muscles and femur. Urinary excretion of pyridinoline was markedly increased as early as 1 day after the initiation of tail-suspension, suggesting that bone resorption is increased in the early stages of skeletal unloading. Indeed, activity of TR-ACP (tartarate resisting acid phosphatase) and serum free calcium concentration increased during the first three days of tail-suspension. Increased serum free calcium, probably due to bone resorption of hindlimb bones r
esulted in the decreased secretion of PTH (parathyroid hormone). Since activation of vitamin D_3 (la-hydroxylation) is increased by PTH,the concentration of 1,25-(OH)_2-vitamin D_3 was also decreased during tail-suspension. The ALP (alkaline phosphatase activity) decreased after 5-day of tail suspension, suggesting that bone formation was suppressed by skeletal unloading at later stage.
In the tail-suspended rats, urinary excretion of corticosterone was increased from Day 1 to 3, indicating that suspension elicited stress response to the rats.
From these results, it is suggested that skeletal unloading causes early increase in bone resorption, resulting in the suppression of PTH secretion and decreased activation of vitamin D_3. Increased glucocorticoid secretion from the adrenocortical cells exerts strong catabolic action on muscle and bones. It is conclude that these combined response of endocrine system aggravates the disuse atrophy caused by skeletal unloading.
II) Study using aged (18 month old) rats
In the aged rats, tail-suspension for 1-2 weeks caused the atrophy of antigravity muscles as observed in the young rats. However, no atrophy of hindlimb bone was observed. Determination of ALP and TR-ACP activities in the femur revealed that the activity in the aged, non-suspended control was much less that of the young control rats. No alteration of the enzyme activities by tail-suspension was observed in the aged rats. These results suggest that bone remodeling in the aged rats is extremely low.
In the aged rats, urinary excretion of corticosterone was 15 times higher than that in the young rats even before the tail-suspension. Furthermore, no increase of corticosterone was observed after the initiation of tail-suspension, suggesting the alteration of hypothalamo-pituitary-adrenocortical regulation by aging. Less