Genetic loci for bone architecture determined by three-dimensional CT in crosses with the diabetic GK rat

Lagerholm, Sofia; Park, Hee-Bok; Luthman, Holger; Nilsson, Mats A; McGuigan, Fiona; Swanberg, Maria; Åkesson, Kristina

doi:10.1016/j.bone.2010.08.003

Cited by 5 publications

(7 citation statements)

References 51 publications

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“…Several QTLs identified in this study co-localized with our previously reported QTLs linked to tibial bone phenotypes obtained from pQCT and 3D CT [23], [24] and were in many cases influenced by sex- and reciprocal cross (Table 4). The region on chromosome 1 (17–79 cM) linked to multiple phenotypes obtained from all four methods (pQCT, 3D CT, 3PB and DXA) in both males and females showed predominantly higher significance in the reciprocal cross 1 carrying GK mtDNA.…”

Section: Discussionsupporting

confidence: 76%

“…Previously, we reported results from a genome-wide screen for bone size and trabecular and cortical bone structure of tibia in the same F2 progeny [23], [24]. The biomechanical testing reported here provides bone phenotypes directly reflecting the ability of bone to resist fracture.…”

Section: Discussionmentioning

confidence: 73%

“…In our previous studies using reciprocal F2 crosses from inbred diabetic GK and non-diabetic F344 rats, we reported results from a genome-wide screen for size, trabecular and cortical bone structure of tibia [23], [24]. We identified several significant QTLs for both bone size and structure and additionally found evidence of sex- and reciprocal cross-specific interactions with bone traits.…”

Section: Introductionmentioning

confidence: 79%

“…QTLs linked to 3D-CT and pQCT phenotypes are reported in references [23], [24].fFemale-specific QTL;cCross-specific QTL. The strongest linkage detected in either sex or reciprocal cross is marked in bold.…”

Section: Resultsmentioning

confidence: 99%

“…The instrument was calibrated daily using the manufacturer's phantom. Additionally, we refer to previously reported phenotypes obtained from three-dimensional computed tomography (3D CT) and peripheral quantitative CT (pQCT) [23], [24].…”

Section: Methodsmentioning

confidence: 99%

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Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength

et al. 2011

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Susceptibility to osteoporotic fracture is influenced by genetic factors that can be dissected by whole-genome linkage analysis in experimental animal crosses. The aim of this study was to characterize quantitative trait loci (QTLs) for biomechanical and two-dimensional dual-energy X-ray absorptiometry (DXA) phenotypes in reciprocal F2 crosses between diabetic GK and normo-glycemic F344 rat strains and to identify possible co-localization with previously reported QTLs for bone size and structure. The biomechanical measurements of rat tibia included ultimate force, stiffness and work to failure while DXA was used to characterize tibial area, bone mineral content (BMC) and areal bone mineral density (aBMD). F2 progeny (108 males, 98 females) were genotyped with 192 genome-wide markers followed by sex- and reciprocal cross-separated whole-genome QTL analyses. Significant QTLs were identified on chromosome 8 (tibial area; logarithm of odds (LOD) = 4.7 and BMC; LOD = 4.1) in males and on chromosome 1 (stiffness; LOD = 5.5) in females. No QTLs showed significant sex-specific interactions. In contrast, significant cross-specific interactions were identified on chromosome 2 (aBMD; LOD = 4.7) and chromosome 6 (BMC; LOD = 4.8) for males carrying F344mtDNA, and on chromosome 15 (ultimate force; LOD = 3.9) for males carrying GKmtDNA, confirming the effect of reciprocal cross on osteoporosis-related phenotypes. By combining identified QTLs for biomechanical-, size- and qualitative phenotypes (pQCT and 3D CT) from the same population, overlapping regions were detected on chromosomes 1, 3, 4, 6, 8 and 10. These are strong candidate regions in the search for genetic risk factors for osteoporosis.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength

et al. 2011

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Skeletal biology over the life span: A view from the surfaces

Gosman

Stout

Larsen

2011

American J Phys Anthropol

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The biocultural interpretation of skeletal remains is based upon the foundation of skeletal biology. In this review we examine the current state of skeletal biology research outside of the mainstream anthropology literature. The focus is on the structural changes of bone development and growth, and modeling and repair in the four bone surfaces: periosteal, Haversian, endosteal, and trabecular. The pattern of skeletal changes is placed within the framework of the human life span. New perspectives and direction of research on the environmental, biological, and genetic influences on modeling and remodeling processes are discussed chronologically at each bone surface. Implications for biological anthropologists are considered. This approach emphasizes variation in skeletal biology as a dynamic record of development, maturity, and aging. Skeletal biology has taken on a central role in a range of research areas that pertain to living and past primates, including humans. In this review we aim to examine the current state of understanding of skeletal biology, linking the morphology and structural changes of bone development, growth, remodeling, and repair within, on, and between the four surfaces of bone: periosteal, cortical/haversian, endosteal, and trabecular. The pattern of changes is placed within the framework of the human life span. Of specific interest are the age-associated and bone surface-specific influences of hormonal changes, the molecular and biochemical microenvironment of bone, and the mechanical environment on bone density, geometry, and microarchitecture. These types of biological data intersect with skeletal growth, development, and bone maintenance. The variations and perturbations of these processes provide physical anthropologists the opportunities and tools to interpret biocultural and behavioral aspects of ancient and recent human groups, such as bone mass accrual during subadult years and bone loss in later years. This contribution to the anthropological skeletal biology literature underscores the highly dynamic nature of skeletal tissues. It references the growing recognition that the mechanical and nutrient environment strongly influences bone beginning in utero and continues throughout life. Our goal is not to provide an exhaustive review of the bone biology or related bioanthropology literature, but rather to provide research perspectives currently being explored by bone science outside of anthropology-specific literature, that contribute to the growing discussion of the such issues as development and aging. BONE ENVELOPES AND THEIR SURFACESBone is composed of two major compartments or envelopes in which modeling and remodeling occur, namely periosteal and endocortical. These, in turn, have the following available surfaces: periosteal, intracortical, endosteal, and trabecular (Martin et al., 1998; see Fig. 1). The modeling process involves the independent actions of bone formation and bone resorption on different surfaces, whereas the remodeling process involves the sequentially sy...

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