Expression of muscle anabolic and metabolic factors in mechanically loaded MLO-Y4 osteocytes

Lack of physical activity results in muscle atrophy and bone loss, which can be counteracted by mechanical loading. Similar molecular signaling pathways are involved in the adaptation of muscle and bone mass to mechanical loading. Whether anabolic and metabolic factors regulating muscle mass, i.e., insulin-like growth factor-I isoforms (IGF-I Ea), mechano growth factor (MGF), myostatin, vascular endothelial growth factor (VEGF), or hepatocyte growth factor (HGF), are also produced by osteocytes in bone in response to mechanical loading is largely unknown. Therefore, we investigated whether mechanical loading by pulsating fluid flow (PFF) modulates the mRNA and/or protein levels of muscle anabolic and metabolic factors in MLO-Y4 osteocytes. Unloaded MLO-Y4 osteocytes expressed mRNA of VEGF, HGF, IGF-I Ea, and MGF, but not myostatin. PFF increased mRNA levels of IGF-I Ea (2.1-fold) and MGF (2.0-fold) at a peak shear stress rate of 44Pa/s, but not at 22Pa/s. PFF at 22 Pa/s increased VEGF mRNA levels (1.8- to 2.5-fold) and VEGF protein release (2.0- to 2.9-fold). Inhibition of nitric oxide production decreased (2.0-fold) PFF-induced VEGF protein release. PFF at 22 Pa/s decreased HGF mRNA levels (1.5-fold) but increased HGF protein release (2.3-fold). PFF-induced HGF protein release was nitric oxide dependent. Our data show that mechanically loaded MLO-Y4 osteocytes differentially express anabolic and metabolic factors involved in the adaptive response of muscle to mechanical loading (i.e., IGF-I Ea, MGF, VEGF, and HGF). Similarly to muscle fibers, mechanical loading enhanced expression levels of these growth factors in MLO-Y4 osteocytes. Although in MLO-Y4 osteocytes expression levels of IGF-I Ea and MGF of myostatin were very low or absent, it is known that the activity of osteoblasts and osteoclasts is strongly affected by them. The abundant expression levels of these factors in muscle cells, in combination with low expression in MLO-Y4 osteocytes, provide a possibility that growth factors expressed in muscle could affect signaling in bone cells

Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age

<p>Abstract</p> <p>Background</p> <p>Mathematical models can be used to predict individual growth responses to growth hormone (GH) therapy. The aim of this study was to construct and validate high-precision models to predict the growth response to GH treatment of short children, independent of their GH status, birth size and gestational age. As the GH doses are included, these models can be used to individualize treatment.</p> <p>Methods</p> <p>Growth data from 415 short prepubertal children were used to construct models for predicting the growth response during the first years of GH therapy. The performance of the models was validated with data from a separate cohort of 112 children using the same inclusion criteria.</p> <p>Results</p> <p>Using only auxological data, the model had a standard error of the residuals (SD_res), of 0.23 SDS. The model was improved when endocrine data (GH_maxprofile, IGF-I and leptin) collected before starting GH treatment were included. Inclusion of these data resulted in a decrease of the SD_resto 0.15 SDS (corresponding to 1.1 cm in a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a separate cohort, showed similar SD_resfor both types of models. Preterm children were not included in the Model group, but predictions for this group were within the expected range.</p> <p>Conclusion</p> <p>These prediction models can with high accuracy be used to identify short children who will benefit from GH treatment. They are clinically useful as they are constructed using data from short children with a broad range of GH secretory status, birth size and gestational age.</p

Is breastfeeding related to bone properties? A longitudinal analysis of associations between breastfeeding duration and pQCT parameters in children and adolescents

Nutritive and bioactive components of human milk could be involved in programming metabolic systems that affect bone growth throughout the life course. Bone properties in childhood and adolescence might differ, depending on breastfeeding duration. Thus, breastfeeding could be a relevant factor in the context of primary osteoporosis prevention. The prospective association between breastfeeding duration and bone properties was investigated using the data of 284 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study. Breastfeeding duration was assessed during infancy. Bone properties were measured by peripheral quantitative computed tomography (pQCT) at ages 5-23 years. Cortical volumetric bone mineral density, cortical bone mineral content, strength strain index, total cross-sectional area of the bone and cross-sectional area of the cortical bone were determined at the 65% site of the radius. Linear regression analyses were performed to check for differences in pQCT parameters of subjects who had not or shortly been breastfed (0-16 weeks) and subjects who had been breastfed for a long duration (17 weeks). Multivariable models adjusted for age, gender, forearm length, muscle cross-sectional area, body mass index standard deviation score (SDS), height SDS and socio-economic status did not yield associations between breastfeeding duration and pQCT parameters. These findings suggest neither protective nor adverse effects of prolonged breastfeeding on bone health in childhood and adolescence. Influences of early nutrition on bone growth might be overridden by current effects of mechanical loads on bone physiology