The hunger games of skeletal metabolism

Wee, Natalie K.Y.; Baldock, Paul A.

doi:10.1038/bonekey.2014.83

Cited by 6 publications

(4 citation statements)

References 70 publications

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“…Accordingly, ghrelin levels in the blood of our KOs are significantly higher than in the WTs as tested by ELISA (Figure 4C ). Closing the circle, the literature tells us that ghrelin promotes bone formation either through the induction of growth hormone or through growth hormone-independent mechanisms (Tong et al, 2012 ; Delhanty et al, 2014b ; Wee and Baldock, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

“…Low glycemic levels induce ghrelin secretion in the stomach through sympathetic neurons and the release of norepinephrine (Goldstein et al, 2011 ). Then ghrelin favors bone formation either in a direct way acting on osteoblasts (Ma et al, 2015 ) or through the induction of growth hormone or IGF-1 (Fukushima et al, 2005 ; Deng et al, 2008 ; Tong et al, 2012 ; Delhanty et al, 2014a , b ; Wee and Baldock, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

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Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

et al. 2016

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Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

et al. 2016

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“…Ghrelin, a 28-amino acid predominantly produced by the gastric mucosa [ 13 ], has been shown to display appetite-stimulatory effects and induces a positive energy balance leading to body weight gain. Leptin and ghrelin antagonize each other in regulating energy balance [ 14 ]. A number of studies have reported serum leptin and ghrelin level disorders in AIS patients [ 15 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls

Zhang

Zhou

et al. 2018

BioMed Research International

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Background Adolescent idiopathic scoliosis (AIS) is common deformity with unknown cause. Previous studies have suggested the abnormal serum leptin and ghrelin level in AIS girls. The aim of present study was to evaluate whether the serum leptin and ghrelin level could serve as risk factor in predicting the curve progression in AIS girls. The associations between them and the physical characteristics were also investigated. Materials and Methods Circulating leptin and ghrelin levels from 105 AIS girls and 40 age-matched non-AIS girls were examined by enzyme-linked immunosorbent assay. The correlations between ghrelin and leptin levels and growth-related parameters (age, weight, corrected height, corrected BMI, main Cobb angle, and Risser sign) were analyzed in AIS group. Multivariate logistic regression was used to investigate factors predicting curve progression in AIS girls. Results A significantly lower leptin level (6.55 ± 2.88 vs. 8.01 ± 3.12 ng/ml, p < 0.05) and a higher ghrelin level (6.33 ± 2.46 vs. 4.46 ± 2.02 ng/ml, p < 0.05) were found in all AIS patients, as compared with normal controls. Curve progression patients had a higher ghrelin level than stable curve patients (7.61 ± 2.48 vs. 5.54 ± 2.11 ng/ml, p < 0.01); for leptin level, there was no significant difference between progression and stable group. The results of multivariate logistic stepwise regression showed that premenarche status, initial main Cobb magnitude that was more than or equal to 23°, high ghrelin level (≥7.30 ng/ml), and lower Risser grade (grades 0 to 2) were identified as risk factors in predicting curve progression. Ghrelin levels of >6.48 ng/ml were predictive for curve progression with 70.00 % sensitivity and 72.31 % specificity, and the area under the curve (AUC) was 0.741 (95 % confidence interval 0.646-0.821). Conclusions High ghrelin level may serve as a new quantitative indicator for predicting curve progression in AIS girls.

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“…In addition, we also measured the serum levels of adiponectin and VEGF. Adiponectin has been identified in osteoblasts and osteoclasts, but the effects of adiponectin on bone mechanism still remain unclear 23 . VEGF is a promoter for osteoblast differentiation and bone mineralization 24 .…”

Section: Resultsmentioning

confidence: 99%

Paradoxical Response to Mechanical Unloading in Bone Loss, Microarchitecture, and Bone Turnover Markers

Sun¹,

Yang²,

Wang³

et al. 2015

Int. J. Med. Sci.

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Background: Sclerostin, encoded by the SOST gene, has been implicated in the response to mechanical loading in bone. Some studies demonstrated that unloading leads to up-regulated SOST expression, which may induce bone loss.Purpose: Most reported studies regarding the changes caused by mechanical unloading were only based on a single site. Considering that the longitudinal bone growth leads to cells of different age with different sensitivity to unloading, we hypothesized that bone turnover in response to unloading is site specific.Methods: We established a disuse rat model by sciatic neurectomy in tibia. In various regions at two time-points, we evaluated the bone mass and microarchitecture in surgically-operated rats and control rats by micro-Computed Tomography (micro-CT) and histology, sclerostin/SOST by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (qPCR), tartrate resistant acid phosphatase 5b (TRAP 5b) by ELISA and TRAP staining, and other bone markers by ELISA. Results: Micro-CT and histological analysis confirmed bone volume in the disuse rats was significantly decreased compared with those in the time-matched control rats, and microarchitecture also changed 2 and 8 weeks after surgery. Compared with the control groups, SOST mRNA expression in the diaphysis was down-regulated at both week 2 and 8. On the contrary, the percentage of sclerostin-positive osteocytes showed an up-regulated response in the 5 - 6 mm region away from the growth plate, while in the 2.5 - 3.5 mm region, the percentage was no significant difference. Nevertheless, in 0.5 - 1.5 mm region, the percentage of sclerostin-positive osteocytes decreased after 8 weeks, consistent with serum SOST level. Besides, the results of TRAP also suggested that the expression in response to unloading may be opposite in different sites or system.Conclusion: Our data indicated that unloading-induced changes in bone turnover are probably site specific. This implies a more complex response pattern to unloading and unpredictable therapeutics which target SOST or TRAP 5b.

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The hunger games of skeletal metabolism

Cited by 6 publications

References 70 publications

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls

Paradoxical Response to Mechanical Unloading in Bone Loss, Microarchitecture, and Bone Turnover Markers

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