scholarly journals The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation

2021 ◽  
Vol 12 ◽  
Author(s):  
Dung-Jang Tsai ◽  
Wen-Hui Fang ◽  
Li-Wei Wu ◽  
Ming-Cheng Tai ◽  
Chung-Cheng Kao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Mass ◽  
Mrna Expression ◽  
Binding Site ◽  
Binding Affinity ◽  
Mass Density ◽  
Case Control ◽  
Luciferase Reporter ◽  
Bone Mass Density ◽  
Genome Wide Association Studies

PurposeGenome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP).MethodsWe performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment.ResultsThrough candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23–21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen’s q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05).ConclusionsOur results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.

The impact of the metabolic syndrome on bone mass density: a prospective case control study

2017 ◽  
Vol 33 (3) ◽  
Author(s):  
Eleni Alhazidou ◽  
Vasilios Pergialiotis ◽  
Periklis Panagopoulos ◽  
Charalampos Chrelias ◽  
Erifili Hatziagelaki ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Bone Mass ◽  
Case Control Study ◽  
Mass Density ◽  
Case Control ◽  
Bone Mass Density ◽  
Menopausal Women ◽  
Turnover Markers ◽  
Control Study ◽  
Prospective Case Control Study

AbstractBackgroundObesity and metabolic syndrome (MetS) during the perimenopausal period and in menopause have been linked to altered bone mass density (BMD) in various experimental studies. However, current clinical studies provide conflicting results in this field. The purpose of the present study was to evaluate this association.Materials and methodsWe conducted a prospective case control study that was based on a consecutive series of menopausal women who attended the Reproductive Endocrinology Outpatient Clinic of our hospital between January 2013 and December 2016.ResultsOne hundred and forty post-menopausal women were included in the present study. After stratifying the women in two groups according to the presence of MetS we observed that bone turnover markers remained unaffected by the presence of MetS (p > 0.05). On the other hand, both the T- and Z-scores of women with MetS were significantly higher compared to healthly postmenopausal women [T-score: 0.4 (−0.7 to 1.3) vs. −1 (−1.62 to −0.1), p < 0.001] [Z-score: 0.55 (−0.3 to 1.7) vs. −0.4 (−1.1 to 0.4), p = 0.003].ConclusionsAccording to the findings of our study the presence of MetS during the perimenopausal years seems to have a mild benefit on bone mass density. The pathophysiology that underlies this effect remains unclear as bone turnover markers seem to be unaffected by MetS.

scholarly journals The influence of bone quality on radiological outcome in 50 consecutive acetabular fractures treated with a pre-contoured anatomic suprapectineal plate

2021 ◽  
Author(s):  
Maximilian J. Hartel ◽  
Tareq Naji ◽  
Florian Fensky ◽  
Frank O. Henes ◽  
Darius M. Thiesen ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Bone Mass ◽  
Bone Quality ◽  
Hip Arthroplasty ◽  
Mass Density ◽  
Acetabular Fractures ◽  
Bone Mass Density ◽  
Radiological Outcome ◽  
Total Hip ◽  
The Impact

Abstract Purpose To investigate the range of indications of an anatomical-preshaped three-dimensional suprapectineal plate and to assess the impact of the bone mass density on radiologic outcomes in different types of acetabular fractures. Patients and methods A consecutive case series of 50 acetabular fractures (patient age 69 ± 23 years) treated with suprapectineal anatomic plates were analyzed in a retrospective study. The analysis included: Mechanism of injury, fracture pattern, surgical approach, need for additional total hip arthroplasty, intra- or postoperative complications, as well as bone mass density and radiological outcome on postoperative computed tomography. Results Most frequently, anterior column fracture patterns with and without hemitransverse components as well as associated two column fractures were encountered. The anterior intrapelvic approach (AIP) was used in 98% (49/50) of the cases as primary approach with additional utilization of the first window of the ilioinguinal approach in 13/50 cases (26%). Determination of bone density revealed impaired bone quality in 70% (31/44). Postoperative steps and gaps were significantly greater in this subgroup (p < 0.05). Fracture reduction quality for postoperative steps revealed anatomic results in 92% if the bone quality was normal and in 46% if impaired (p < 0.05). In seven cases (14%), the plate was utilized in combination with acute primary arthroplasty. Conclusion A preshaped suprapectineal plate provides good radiological outcomes in a variety of indications in a predominantly geriatric cohort. Impaired bone quality has a significantly higher risk of poor reduction results. In cases with extensive joint destruction, the combination with total hip arthroplasty was a valuable option.

Relationship between bone mass density and tensile strength of the skin in women

2001 ◽  
Vol 31 (8) ◽  
pp. 731-735 ◽  
Author(s):  
G. E. Piérard ◽  
C. Piérard-Franchimont ◽  
S. Vanderplaetsen ◽  
N. Franchimont ◽  
U. Gaspard ◽  
...  
Keyword(s):  
Tensile Strength ◽  
Bone Mass ◽  
Mass Density ◽  
Bone Mass Density

scholarly journals Effect of ghrelin on bone mass density: The InChianti study

Bone ◽  
2011 ◽  
Vol 49 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Nicola Napoli ◽  
Claudio Pedone ◽  
Paolo Pozzilli ◽  
Fulvio Lauretani ◽  
Stefania Bandinelli ◽  
...  
Keyword(s):  
Bone Mass ◽  
Mass Density ◽  
Bone Mass Density

scholarly journals Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Body Weight ◽  
Bone Loss ◽  
Bone Mass ◽  
Bone Turnover ◽  
Cancellous Bone ◽  
Mass Density ◽  
Female Rats ◽  
Bone Mass Density ◽  
Age Related

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

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