Combination of Weight-Bearing Training and Anti-MSTN Polyclonal Antibody Improve Bone Quality In Rats

Abstract

Weight-bearing exercise is beneficial to bone health. Myostatin (MSTN) deficiency has a positive effect on bone formation. We wondered if a combination of weight-bearing training and polyclonal antibody for MSTN (MsAb) would augment bone formation to a greater degree than single treatment. In this study, rats were randomly assigned to four groups: Control, weight-bearing training (WT), MsAb, and WT+MsAb. The trained rats ran at 15 m/min bearing with 35% of their body weight, 40 min/day (2 min of running followed by 2 min of rest), 6 days/week, for 8 weeks. The rats with MsAb were injected once a week with MsAb for 8 weeks. MicroCT analysis showed that compared with the MsAb group, WT+MsAb significantly enhanced cortical bone mineral density (BMD) (p < .01), bone volume over total volume (BV/TV) (p < .01), trabecular thickness (p < .05), and reduced trabecular separation (Tb.Sp) (p < .01). Compared with the WT group, WT+MsAb significantly increased trabecular BMD (p < .05), BV/TV (p < .05), and decreased Tb.Sp (p < .05). Three-point bending test demonstrated that MsAb failed to improve bone biomechanical properties (p > .05), weight-bearing training significantly increased energy absorption (p < .05) and elastic modulus (p < .05). However, when they combined, biomechanical properties including maximum load (p < .05), stiffness (p < .05), elastic modulus (p < .01) and energy absorption (p < .01) were all significantly enhanced. In conclusion, the combination of weight-bearing training and MsAb have a greater positive effect on bone than treatment with either MsAb or weight-bearing training alone, suggesting that resistance training in combination with MSTN antagonists could be an effective approach for improving bone health and reducing osteoporosis risk.

Effect of exercise on bone in poorly controlled type 1 diabetes mediated by the ActRIIB/Smad signaling pathway

“…Total RNA was isolated using TRIzol reagents (Invitrogen; Thermo Fisher Scientific, Inc., Waltham, MA, USA) according to the manufacturer's instructions, and then it was reverse-transcribed using a PrimeScript™ II 1st Strand cDNA Synthesis kit (Takara Shuzo, Shiga, Japan) (19). Briefly, the RNA with 2 µg was added to 12 µl reaction system of reverse transcription (including 1 µl oligo(dT) 18 ) and then placed in PCR amplifier at 70˚C for 5 min. Then the above system was added in order 4 µl 5xbuffer, 2 µl 10 mM dNTPs, 1 µl RNA inhibitor and 1 µl reverse transcriptase and placed in PCR amplifier at 42˚C for 60 min, the reaction was ended at 80˚C for 5 min.…”

“…Furthermore, it plays a role in regulating bone mass (16). Our previous studies showed that ladder-climbing training could prevent bone loss in diet-induced obese rats by inhibiting MSTN expression (17,18); meanwhile, MSTN is not expressed and secreted in osteoblasts. Active MSTN binds to ActRIIB and could lead to the subsequent phosphorylation of Smad proteins and the initiation of gene expression, so we wondered if exercise could modulate bone metabolism in streptozocin (STZ)-induced diabetes through the inhibition of MSTN.…”

Does Physical Exercise Always Improve Bone Quality in Rats?

“…To generate a more intense exercise and/or load, the principle of weight bearing was applied on the vertebrae of animals. A backpack, representing up to 20% of body weight of the animal tested, was used during the whole running session [ 84 , 85 , 86 , 87 , 88 , 89 ].…”

Therapeutic approaches to osteosarcopenia: insights for the clinician

“…78 Antimyostatin antibodies Antimyostatin antibody in combination with resistance exercise improved bone health in rats. 79 (1) Antimyostatin antibodies increased muscle mass and strength in mice. 80 (2) Antimyostatin antibodies increased lean mass and may improve functional measures of muscle power.…”

“…80 In phase II trials in older adults (aged ⩾75 years) with a history of fall, antimyostatin antibodies increased the lean body mass and mildly improved functional measures associated with muscle strength. 81 Regarding role of myostatin antibodies in improving bone health, data from animal studies indicate that in combination with resistant exercise, myostatin antibodies improved bone mass, 79 however, this effect has not been confirmed in clinical trials.…”