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Oral arginine improves linear growth of long bones and the neuroendocrine mechanism.

ABSTRACT: To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway.Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water (0.045 g L-arginine was mixed with 1 mL water) and administered in rats (10 mL/kg) through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteoclast surface of the femur. Serum growth hormone (GH) concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase (nNOS), soluble guanylyl cyclases (sGCα1 and sGCβ1), growth hormone-releasing hormone (Ghrh) and somatostatin (SS) in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels of nNOS, sGCα1 and sGCβ1 in hypothalamus.After treatment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased (P < 0.05), and serum GH concentration was elevated (P < 0.05). Besides, mRNA and protein levels of nNOS and sGCα1 (P < 0.05), as well as the expression of Gh mRNA (P < 0.01), were significantly up-regulated, while the expression of SS mRNA was down-regulated (P < 0.05).Oral administration of arginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.

SUBMITTER: Jiang MY

PROVIDER: S-EPMC5560364 | biostudies-other | 2011 Jun

REPOSITORIES: biostudies-other

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Project description:One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.

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Oral arginine improves linear growth of long bones and the neuroendocrine mechanism.

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