Dysregulation of the ghrelin/RANKL/OPG pathway in bone mass is related to AIS osteopenia

Xiao, Lairong; Zhang, Hongqi; Wang, Yunjia; Li, Jiong; Yang, Guanteng; Wang, Longjie; Liang, Zhuotao

doi:10.1016/j.bone.2020.115291

Cited by 14 publications

(30 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The extracted information from each paper, including first author, year of publication, number of cases and controls, and mean levels of leptin and ghrelin, is shown in Table 1 . Among these included 9 articles, 6 articles explored changes of serum leptin and sOB-R in AIS [ 11 , 12 , 17 – 19 ], another 2 explored changes of ghrelin in AIS [ 21 , 22 ], while the remaining one study both leptin and ghrelin in AIS [ 20 ]. A total of 700 AIS patients and 3536 healthy controls were included for the meta-analysis of leptin, while 198 AIS patients and 138 healthy controls were included for ghrelin analysis.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, Yu et al reported that high ghrelin could serve as a quantitative indicator for predicting curve progression and thus helps in precise selection of treatment in AIS patients [ 20 ]. Xiao et al observed on significant difference in four ghrelin level-related single nucleotide polymorphisms (SNPs) between the AIS osteopenia and control groups, which indicated that abnormally high ghrelin may not result from gene variations, while dysregulation of ghrelin/receptor activator of nuclear factor-kappa beta ligand (RANKL)/osteoprotegerin (OPG) pathway may lead to decreased osteogenic ability of osteoblasts and bone marrow stem cells (BMSCs), which may be related to lower bone mass in AIS osteopenia [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis

Wang

et al. 2020

J Orthop Surg Res

View full text Add to dashboard Cite

Background Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis. Methods We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI). Results Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of − 0.95 (95% CI − 1.43 to − 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively. Conclusion Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis

Wang

et al. 2020

J Orthop Surg Res

View full text Add to dashboard Cite

show abstract

“…Numerous articles have investigated the relationship between ghrelin and bone mineral density (BMD) with inconsistent results. Xiao et al suggested a dysregulation of ghrelin-regulated pathways that decreases the osteogenic ability of osteoblasts in patients with AIS osteopenia, although they only measured total ghrelin [ 15 ]. Although little is known, there may be differential roles between AG and UAG in BMD.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the same team reported that ghrelin upregulated the expression of specific genes in the chondrocytes of AIS adolescents, which can lead to abnormal cartilage development [ 14 ]. In 2020, Xiao and colleagues showed dysregulation of the ghrelin/RANKL/OPG pathway in AIS adolescents, which can contribute to osteopenia [ 15 ]. Our recent study showed that, in vitro, ghrelin stimulates differentiation and mineralization of mature osteoblasts through the GHSR/GI/cAMP pathway.…”

Section: Introductionmentioning

confidence: 99%

Is ghrelin a biomarker of early-onset scoliosis in children with Prader–Willi syndrome?

Alfaro

Diene

Pinto

et al. 2021

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Adolescents with idiopathic scoliosis display high ghrelin levels. As hyperghrelinemia is found in patients with PWS and early-onset scoliosis (EOS) is highly prevalent in these patients, our aims were to explore (1) whether ghrelin levels differ between those with and without EOS and correlate with scoliosis severity, and (2) whether ghrelin levels in the first year of life are associated with the later development of EOS. Methods We used a case control study design for the first question and a longitudinal design for the second. Patients with PWS having plasma ghrelin measurements recorded between 2013 and 2018 in our database were selected and 30 children < 10 years old with EOS and 30 age- and BMI-matched controls without EOS were included. The Cobb angle at diagnosis was recorded. In addition, 37 infants with a ghrelin measurement in the first year of life were followed until 4 years of age and assessed for EOS. Total ghrelin (TG), acylated (AG) and unacylated ghrelin (UAG), and the AG/UAG ratio were analyzed. Results EOS children had an AG/UAG ratio statistically significantly lower than controls. The Cobb angle was positively correlated with TG and UAG. TG and AG in the first year of life were higher in infants who later develop EOS without reaching a statistically significant difference. Conclusions Our results suggest that ghrelin may play a role in the pathophysiology of EOS in PWS. Higher ghrelinemia in the first year of life required careful follow-up for EOS.

show abstract

“…For human primary osteoblast isolation, chopped cancellous bone tissues from the facet joint or posterior column vertebrae were isolated as described before [ 21 ]. In brief, samples were washed with phosphate-buffered solution (PBS) thrice and then incubated with 0.25% trypsin (Gibco, CA, USA) for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Dysregulated Bone Metabolism Is Related to High Expression of miR-151a-3p in Severe Adolescent Idiopathic Scoliosis

Wang

Zhang

Yang

et al. 2020

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Adolescent idiopathic scoliosis (AIS) is a common complex disease, and bone homeostasis plays an important role in its pathogenesis. Recent advances in epigenetic research show that dysregulated miRNAs may participate in the development of orthopedic diseases and AIS. The aim of this study was to detect differentially expressed miRNAs in severe AIS and elucidate the mechanism of miRNA deregulation in the pathogenesis of AIS. In the present study, miRNA expression profiles were detected in severe and mild AIS patients as well as healthy controls by miRNA sequencing. Candidate miRNAs were validated in a larger cohort. Primary osteoblasts from severe AIS patients were extracted and isolated to determine the effect of the candidate miRNAs on bone metabolism. Finally, we determined the methylation level in primary osteoblasts from severe AIS patients. The result showed that miR-151a-3p was overexpressed in severe AIS patients. Reduced GREM1 expression was observed in primary osteoblasts from severe AIS patients. miR-151a-3p directly inhibited GREM1 in primary osteoblasts. Relatively lower methylation levels were detected in primary osteoblasts from severe AIS patients. In conclusion, our study revealed that plasma miR-151a-3p levels may serve as a biomarker for severe AIS. Overexpression of miR-151a-3p may interrupt bone homeostasis via inhibiting GREM1 expression. Our result may provide a new biomarker for the early detection of AIS and increase our understanding of the pathogenesis of AIS.

show abstract

Dysregulation of the ghrelin/RANKL/OPG pathway in bone mass is related to AIS osteopenia

Cited by 14 publications

References 45 publications

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis

Is ghrelin a biomarker of early-onset scoliosis in children with Prader–Willi syndrome?

Dysregulated Bone Metabolism Is Related to High Expression of miR-151a-3p in Severe Adolescent Idiopathic Scoliosis

Contact Info

Product

Resources

About