Voluntary run training but not estradiol deficiency alters the tibial bone-soleus muscle functional relationship in mice

Abstract

The study's objective was to investigate how estrogen deficiency and run training affect the tibial bone-soleus muscle functional relationship in mice. Female mice were assigned into one of two surgical conditions, ovariectomy (OVX) or sham ovariectomy (sham), and one of two activity conditions, voluntary wheel running (Run) or sedentary (Sed). To determine whether differences observed between OVX and sham conditions could be attributed to estradiol (E(2)), additional OVX mice were supplemented with E(2). Tibial bones were analyzed for their functional capacities, ultimate load, and stiffness. Soleus muscles were analyzed for their functional capacities, maximal isometric tetanic force (P(o)), and peak eccentric force. The ratios of bone functional capacities to those of muscle were calculated. The bone functional capacities were affected by both surgical condition and activity but more strongly by surgical condition. Ultimate load and stiffness for the sham group were 7-12% greater than those for OVX animals (P = 0.002), whereas only stiffness was greater for Run than for Sed animals (9%; P = 0.015). The muscle functional capacities were affected by both surgical condition and activity; however, in contrast to the bone, the muscle was more affected by activity. P(o) and peak eccentric force were 10-21% greater for Run than for Sed animals (P < or = 0.016), whereas only P(o) was greater in sham than in OVX animals (9%; P = 0.011). The bone-to-muscle ratios of functional capacities were affected by activity but not by surgical condition or E(2) supplementation. Thus a mismatch of bone-muscle function occurred in mice that voluntarily ran on wheels, irrespective of estrogen status.

TAT-μUtrophin mitigates the pathophysiology of dystrophin and utrophin double-knockout mice

“…We chose to assess the hindlimb dorsiflexor EDL muscle ex vivo for contractility and susceptibility to injury for consistency between this and our previous work (29). Mice were anesthetized with pentobarbital sodium (25 mg/kg BM) and muscles were mounted to a dual-mode muscle lever system (300B-LR; Aurora Scientific) and incubated at 25°C in an oxygenated bath as previously described (1,6,36). Muscles were maintained at a 0.4 g resting tension (Lo) throughout the experiment (as per 34,35).…”

Focus on voluntary run training but not estradiol deficiency alters the tibial bone-soleus muscle functional relationship in mice: fracture and mechanostat

“…The second theory predicts that the increase in muscle strength is protective; that is, muscle acts as a shock absorber to lessen cortical bending and strain during running. With the animal model, Warren et al (14) found that short-term training induced an increase in the strength of muscle relative to bone; however, this did not increase the bone's susceptibility to fracture in direct bending tests of ultimate strength. They concluded that the longer the muscle-to-bone functional capacity mismatch continued to exist, the greater would be the chance for occurrence of a stress fracture.…”

“…It should be noted that all muscle and bone measurements were made before the 12-wk training program. It would be of interest to evaluate changes in muscle and bone during such a training program to see whether the muscle-bone strength imbalance increases, as would be predicted from the study by Warren et al (14).…”

“…IN THIS ISSUE OF the American Journal of Physiology-Regulatory, Integrative, and Comparative Physiology, Warren et al (14) presented the finding that voluntary wheel running in mice increased the muscle-to-bone strength ratio independent of estrogen status. Although there were no detrimental effects of the increased muscle force on bone caused by the muscleto-bone strength imbalance, it was concluded that such an imbalance over time could lead to stress fracture.…”

“…In addition, Warren et al (14) found that the beneficial effects of exercise on bone were similar in ovariectomized and sham mice, despite the fact that ovariectomized mice voluntarily ran five times less distance on a daily basis than sham mice. This has implications for the "mechanostat" theory of bone formation, which refers to the degree to which strains from loading are detected by bone and translated into the process of increased bone formation (5).…”