Effects Of Exercise On Long Bone Growth Of Female Rats And Study Of Its Alterations In Gene Expression Profile

Objective: Puberty is the second growth spurt of skeleton. It is also a critical period for bone response to exercise. During the pubertal period, when taking part in physical activities, bones receive not only the local biomechanical stimulus generated by physical loads, but also the extra endocrine influences of sex hormones, growth hormone (GH) and growth factor-I (IGF-I) which are induced by physical activity, so there is a synthetical stimulus. The purpose of this study is to investigate the effects of different exercise mode on the growth of long bones in the rapidly growing female rats, and to examine the alterations in gene expression profile associated with exercise, in order to provide reference for optimizing the exercise prescription of benefiting the health of children's and adolescents' bones and maximalizing the peak bone mass, especially to investigate the molecular mechanisms of exercise in pubertal bones.Methods: 32 female SD rats (5 weeks old) were randomly assigned to one of four experimental groups: sedentary, prolonged running, prolonged swimming and intermittent running. All the exercise groups underwent 9 weeks of prolonged running, intermittent running on treadmill and prolonged swimming respectively. The tibiaes' parameters of mineralization, structure, histomorphometry, biomechanical properties and others were measured, and the alterations in gene expression profile of femora of rats in intermitted running groups were also examined by gene chips and quantitive real-time PCR.Results: (1) Prolonged running can promote the growth of rats. It can stimulate longitudinal change in linear growth and bone mineral gain, and enhance the material biomechanical property drastically. (2) Prolonged swimming can improve bone development. It can stimulate bone mineralization, increase water in bones. And enhance the structure biomechanical property drastically. (3) Intermitted running can also stimulate mineralization and longitudinal change in the linear growth of bones. It is the only mode that increases the concentration of E₂ and GH in plasma. (4) All the exercise mode can simulate bone formation. The effect of prolonged swimming on bone growth is less obvious than that of prolonged running, and both them can benefit bone biomechanical properties in different ways. After 9-week of exercise, the resulting effect of prolonged running is greater than that of intermitted running, but as to the ongoing stimulation on bone growth, it is less obvious than that of intermitted running. However, they can all enhance the generation of IGF-1.( 5 )In intermitted running group, the signal transmitting and the metabolization of E₂ are active at rest. Exercise suppresses the signal transmitting by IRS pathway of GH and IGF-1. (6) Exercise can upregulate mRNA expression of proteins generated by osteoblasts in its different development stages and stimulate the generation and mineralization of bone matrix. The expression of Runx2 mRNA at rest is not significantly affected by exercise. At the same time, exercise inhabits bone resorption by reducing the generation of V-ATPase. (7)This study first discovers that exercise can increase apoptosis in bone tissue. Exercise can make p53mRNA upregulation and HSP90 mRNA downregulation and induces apoptosis through mitochondrial pathway mediated by Cyt-c and AIF. The apoptosis in bone tissue of the exercise group comes most likely from obsteoclasts and their precursors.Conclusion: All the exercise modes can promote the development and biomechanical properties of female rats' long bones in different ways and at different levels. But it needs longer training period to get BMD or BMC and morphometrics that can be mearsured. Non-weight-bearing exercise and weight-bearing exercise influence the bone growth and biomechanical properties through different ways. The local biomechanical stimulus and systematic stimulus generated by intermittent running are higher than that generated by prolong running, exercise will have stronger effect on bone growth if its intensity is lower than that in this study. The study of gene expression profile suggests that exercise can stimulate bone formation by upragulating the mRNA expression of products of osteoblasts and suppress bone resorption by downregulating the mRNA expression of V-ATPase. Exercise can also increase apoptosis through mitochondrial pathway by changing the mRNA expression of p53 and HSP90. It is maybe the osteoclast linear cells that is increasing apoptosis induced by exercise. So that all make exercise stimulate the long bone growth.