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Weak genetic relationship between trabecular bone morphology and obesity in mice.

ABSTRACT: Obesity, in addition to being associated with metabolic diseases, such as diabetes, has also been found to lower the risk of osteoporotic fractures. The relationship between obesity and bone trabecular structure is complex, involving responses to mechanical loading and the effects of adipocyte-derived hormones, both directly interacting with bone tissue and indirectly through central nervous system signaling. Here we examine the effects of sex, a high fat diet, and genetics on the trabecular density and structure of the lumbar and caudal vertebra and the proximal tibia along with body weight, fat pad weight, and serum leptin levels in a murine obesity model, the LGXSM recombinant inbred (RI) mouse strains. The sample included 481 mice from 16 RI strains. We found that vertebral trabecular density was higher in males while the females had higher tibial trabecular density. The high fat diet led to only slightly higher trabecular density in both sexes despite its extreme effects on obesity and serum leptin levels. Trait heritabilities are moderate to strong and genetic correlations among trabecular features are high. Most genetic variation contrasts strains with large numbers of thick, closely-spaced, highly interconnected, plate-like trabeculae with a high bone volume to total volume ratio against strains displaying small numbers of thin, widely-spaced, sparsely connected, rod-like trabeculae with a low bone volume to total volume ratio. Genetic correlations between trabecular and obesity-related traits were low and not statistically significant. We mapped trabecular properties to 20 genomic locations. Only one-quarter of these locations also had effects on obesity. In this population obesity has a relatively minor effect on trabecular bone morphology.

SUBMITTER: Carson EA

PROVIDER: S-EPMC3371175 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Weak genetic relationship between trabecular bone morphology and obesity in mice.

Carson E Ann EA Kenney-Hunt Jane P JP Pavlicev Mihaela M Bouckaert Kristine A KA Chinn Alex J AJ Silva Matthew J MJ Cheverud James M JM

Bone 20120406 1

Obesity, in addition to being associated with metabolic diseases, such as diabetes, has also been found to lower the risk of osteoporotic fractures. The relationship between obesity and bone trabecular structure is complex, involving responses to mechanical loading and the effects of adipocyte-derived hormones, both directly interacting with bone tissue and indirectly through central nervous system signaling. Here we examine the effects of sex, a high fat diet, and genetics on the trabecular den ...[more]

PMID: 22503703

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Project description:BackgroundTMJ morphology/position and trabecular structure are influenced by various factors. The role of the interincisal angle, an indicator of the anterior occlusal relationship, on TMJ remains unclear. This study aims to investigate the morphology, trabecular bone structure, and position of the condyle, as well as the glenoid fossa's morphology in skeletal class II populations with different interincisal angles.Materials and methodsA total of 150 adult patients with normodivergent facial types and skeletal class II malocclusions were selected and divided into three groups based on their interincisal angles: normal, small, and large angle groups. The indexes of TMJ were measured using cone-beam computed tomography (CBCT) data and analyzed using Dolphin Imaging, Mimics, and ImageJ.ResultsThe small angle group had the smallest anteroposterior diameter (APD), while the large angle group had a greater mediolateral diameter (MLD). The large angle group exhibited significantly the largest maximum axial area, bone surface area, and bone volume (P < 0.05). Small and large angle groups exhibited greater bone trabeculae (Tb. N) and thinner trabecular thickness (Tb. Th). Compared to the normal angle group, the small angle group exhibited a larger horizontal condylar angle and smaller bilateral condylar angles on the axial plane, while the large angle group showed the opposite trend. Small and large angle groups showed a reduced vertical condyle angle on the coronal plane, with the largest reduction observed in the large angle group (P < 0.05). Small and large angle groups had higher heights of the glenoid fossa (GFH). The large angle group exhibited the greatest GFH and width of the glenoid fossa (GFW) (P < 0.05).ConclusionThe large angle group had elongated oval and large condyles, and deeper glenoid fossae, while a flattened-oval and smaller condyle, and wider and shallower glenoid fossae were observed in the small angle group. Small and large interincisal angle affects the structure of condylar trabeculae, resulting in thinner Tb. Th and greater Th. N. In the condylar position, small and large angle groups exhibit condylar rotation in the axial and coronal planes. Therefore, the interincisal angle affects the morphology, position, and trabecular structure of the TMJ. This implies that we must pay attention to the impact of the interincisal angle on TMJ, and it is crucial to restore the normal interincisal angle during orthodontic treatment.

Project description:Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n?=?5,878) followed by replication (n?=?1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p?=?3.6×10?¹?; LOC285735, rs271170, p?=?2.7×10?¹²; OPG, rs7839059, p?=?1.2×10?¹?; and ESR1/C6orf97, rs6909279, p?=?1.1×10??). The trabecular vBMD GWA meta-analysis (n?=?2,500) followed by replication (n?=?1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p?=?1.9×10??). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n?=?729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk.

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Weak genetic relationship between trabecular bone morphology and obesity in mice.

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Weak genetic relationship between trabecular bone morphology and obesity in mice.

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