Assessment of DNA Methylation Patterns in the Bone and Cartilage of a Nonhuman Primate Model of Osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) affects humans and several other animals. Thus, the mechanisms underlying this disorder, such as specific skeletal tissue DNA methylation patterns, may be evolutionary conserved. However, associations between methylation and OA have not been readily studied in nonhuman animals. Baboons serve as important models of disease and develop OA at rates similar to those in humans. Therefore, this study investigated the associations between methylation and OA in baboons to advance the evolutionary understanding of OA. DESIGN: Trabecular bone and cartilage was collected from the medial condyles of adult female baboon femora, 5 with and 5 without knee OA. The Infinium HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation patterns in these tissues. RESULTS: Approximately 44% of the 450K array probes reliably align to the baboon genome, contain a CpG site of interest, and maintain a wide distribution throughout the genome. Of the 2 filtering methods tested, both identified significantly differentially methylated positions (DMPs) between healthy and OA individuals in cartilage tissues, and some of these patterns overlap with those previously identified in humans. Conversely, no DMPs were found between tissue types or between disease states in bone tissues. CONCLUSIONS: Overall, the 450K array can be used to measure genome-wide DNA methylation in baboon tissues and identify significant associations with complex traits. The results of this study indicate that some DNA methylation patterns associated with OA are evolutionarily conserved, while others are not. This warrants further investigation in a larger and more phylogenetically diverse sample set.

Pueraria mirifica extract and puerarin enhance proliferation and expression of alkaline phosphatase and type I collagen in primary baboon osteoblasts.

Phytoestrogen-rich Pueraria mirifica (PM) tuberous extract is a promising candidate for the development of anti-osteoporosis drugs for postmenopausal women, but its action has never been validated in humans or in non-human primates, which are more closely related to humans than rodents. In vitro study of non-human primate osteoblasts is thus fundamental to prepare for in vivo studies of phytoestrogen effects on primate bone. This study aimed to establish a culture system of baboon primary osteoblasts and to investigate the effects of PM extract and its phytoestrogens on these cells. Primary osteoblasts from adult baboon fibulae exhibited osteoblast characteristics in regard to proliferation, differentiation, mineralization, and estrogen receptor expression. They responded to 17ß-estradiol by increased proliferation rate and mRNA levels of alkaline phosphatase (ALP), type I collagen, and osteocalcin. After being exposed for 48 h to 100 µg/ml PM extract, 1000 nM genistein, or 1000 nM puerarin, primary baboon osteoblasts markedly increased the rate of proliferation and mRNA levels of ALP and type I collagen without changes in Runx2, osterix, or osteocalcin expression. PM extract, genistein, and puerarin also decreased the RANKL/OPG ratio, suggesting that they could decrease osteoclast-mediated bone resorption. However, neither PM extract nor its phytoestrogens altered calcium deposition in osteoblast culture. In conclusion, we have established baboon primary osteoblast culture, which is a new tool for bone research and drug discovery. Furthermore, the present results provide substantial support for the potential of PM extract and its phytoestrogens to be developed as therapeutic agents against bone fragility.

Fracture risk predictions based on statistical shape and density modeling of the proximal femur.

Increased risk of skeletal fractures due to bone mass loss is a major public health problem resulting in significant morbidity and mortality, particularly in the case of hip fractures. Current clinical methods based on two-dimensional measures of bone mineral density (areal BMD or aBMD) are often unable to identify individuals at risk of fracture. We investigated predictions of fracture risk based on statistical shape and density modeling (SSDM) methods using a case-cohort sample of individuals from the Osteoporotic Fractures in Men (MrOS) study. Baseline quantitative computed tomography (QCT) data of the right femur were obtained for 513 individuals, including 45 who fractured a hip during follow-up (mean 6.9 year observation, validated by physician review). QCT data were processed for 450 individuals (including 40 fracture cases) to develop individual models describing three-dimensional bone geometry and density distribution. Comparison of mean fracture and non-case models indicated complex structural differences that appear to be responsible for resistance to hip fracture. Logistic regressions were used to model the relation of baseline hip BMD and SSDM weighting factors to the occurrence of hip fracture. Area under the receiver operating characteristic (ROC) curve (AUC) for a prediction model based on weighting factors and adjusted by age was significantly greater than AUC for a prediction model based on aBMD and age (0.94 versus 0.83, respectively). The SSDM-based prediction model adjusted by age correctly identified 55% of the fracture cases (and 94.7% of the non-cases), whereas the clinical standard aBMD correctly identified 10% of the fracture cases (and 91.3% of the non-cases). SSDM identifies subtle changes in combinations of structural bone traits (eg, geometric and BMD distribution traits) that appear to indicate fracture risk. Investigation of important structural differences in the proximal femur between fracture and no-fracture cases may lead to improved prediction of those at risk for future hip fracture.

Baboons as a model to study genetics and epigenetics of human disease.

A major challenge for understanding susceptibility to common human diseases is determining genetic and environmental factors that influence mechanisms underlying variation in disease-related traits. The most common diseases afflicting the US population are complex diseases that develop as a result of defects in multiple genetically controlled systems in response to environmental challenges. Unraveling the etiology of these diseases is exceedingly difficult because of the many genetic and environmental factors involved. Studies of complex disease genetics in humans are challenging because it is not possible to control pedigree structure and often not practical to control environmental conditions over an extended period of time. Furthermore, access to tissues relevant to many diseases from healthy individuals is quite limited. The baboon is a well-established research model for the study of a wide array of common complex diseases, including dyslipidemia, hypertension, obesity, and osteoporosis. It is possible to acquire tissues from healthy, genetically characterized baboons that have been exposed to defined environmental stimuli. In this review, we describe the genetic and physiologic similarity of baboons with humans, the ability and usefulness of controlling environment and breeding, and current genetic and genomic resources. We discuss studies on genetics of heart disease, obesity, diabetes, metabolic syndrome, hypertension, osteoporosis, osteoarthritis, and intrauterine growth restriction using the baboon as a model for human disease. We also summarize new studies and resources under development, providing examples of potential translational studies for targeted interventions and therapies for human disease.

Mechanical contributors to sex differences in idiopathic knee osteoarthritis.

The occurrence of knee osteoarthritis (OA) increases with age and is more common in women compared with men, especially after the age of 50 years. Recent work suggests that contact stress in the knee cartilage is a significant predictor of the risk for developing knee OA. Significant gaps in knowledge remain, however, as to how changes in musculoskeletal traits disturb the normal mechanical environment of the knee and contribute to sex differences in the initiation and progression of idiopathic knee OA. To illustrate this knowledge deficit, we summarize what is known about the influence of limb alignment, muscle function, and obesity on sex differences in knee OA. Observational data suggest that limb alignment can predict the development of radiographic signs of knee OA, potentially due to increased stresses and strains within the joint. However, these data do not indicate how limb alignment could contribute to sex differences in either the development or worsening of knee OA. Similarly, the strength of the knee extensor muscles is compromised in women who develop radiographic and symptomatic signs of knee OA, but the extent to which the decline in muscle function precedes the development of the disease is uncertain. Even less is known about how changes in muscle function might contribute to the worsening of knee OA. Conversely, obesity is a stronger predictor of developing knee OA symptoms in women than in men. The influence of obesity on developing knee OA symptoms is not associated with deviation in limb alignment, but BMI predicts the worsening of the symptoms only in individuals with neutral and valgus (knock-kneed) knees. It is more likely, however, that obesity modulates OA through a combination of systemic effects, particularly an increase in inflammatory cytokines, and mechanical factors within the joint. The absence of strong associations of these surrogate measures of the mechanical environment in the knee joint with sex differences in the development and progression of knee OA suggests that a more multifactorial and integrative approach in the study of this disease is needed. We identify gaps in knowledge related to mechanical influences on the sex differences in knee OA.

Microstructure and nanomechanical properties in osteons relate to tissue and animal age.

Material property changes in bone tissue with ageing are a crucial missing component in our ability to understand and predict age-related fracture. Cortical bone osteons contain a natural gradient in tissue age, providing an ideal location to examine these effects. This study utilized osteons from baboons aged 0-32 years (n=12 females), representing the baboon lifespan, to examine effects of tissue and animal age on mechanical properties and composition of the material. Tissue mechanical properties (indentation modulus and hardness), composition (mineral-to-matrix ratio, carbonate substitution, and crystallinity), and aligned collagen content (aligned collagen peak height ratio) were sampled along three radial lines in three osteons per sample by nanoindentation, Raman spectroscopy, and second harmonic generation microscopy, respectively. Indentation modulus, hardness, mineral-to-matrix ratio, carbonate substitution, and aligned collagen peak height ratio followed biphasic relationships with animal age, increasing sharply during rapid growth before leveling off at sexual maturity. Mineral-to-matrix ratio and carbonate substitution increased 12% and 6.7%, respectively, per year across young animals during growth, corresponding with a nearly 7% increase in stiffness and hardness. Carbonate substitution and aligned collagen peak height ratio both increased with tissue age, increasing 6-12% across the osteon radii. Indentation modulus most strongly correlated with mineral-to-matrix ratio, which explained 78% of the variation in indentation modulus. Overall, the measured compositional and mechanical parameters were the lowest in tissue of the youngest animals. These results demonstrate that composition and mechanical function are closely related and influenced by tissue and animal age.

Statistical shape modeling describes variation in tibia and femur surface geometry between Control and Incidence groups from the osteoarthritis initiative database.

We hypothesize that variability in knee subchondral bone surface geometry will differentiate between patients at risk and those not at risk for developing osteoarthritis (OA) and suggest that statistical shape modeling (SSM) methods form the basis for developing a diagnostic tool for predicting the onset of OA. Using a subset of clinical knee MRI data from the osteoarthritis initiative (OAI), the objectives of this study were to (1) utilize SSM to compactly and efficiently describe variability in knee subchondral bone surface geometry and (2) determine the efficacy of SSM and rigid body transformations to distinguish between patients who are not expected to develop osteoarthritis (i.e. Control group) and those with clinical risk factors for OA (i.e. Incidence group). Quantitative differences in femur and tibia surface geometry were demonstrated between groups, although differences in knee joint alignment measures were not statistically significant, suggesting that variability in individual bone geometry may play a greater role in determining joint space geometry and mechanics. SSM provides a means of explicitly describing complete articular surface geometry and allows the complex spatial variation in joint surface geometry and joint congruence between healthy subjects and those with clinical risk of developing or existing signs of OA to be statistically demonstrated.

Cross-sectional geometry of the femoral midshaft in baboons is heritable.

A great deal of research into the determinants of bone strength has unequivocally demonstrated that variation in bone strength is highly subject to genetic factors. Increasing attention in skeletal genetic studies is being paid to indicators of bone quality that complement studies of BMD, including studies of the genetic control of bone geometry. The aim of this study is to investigate the degree to which normal population-level variation in femoral midshaft geometry in a population of pedigreed baboons (Papio hamadryas spp.) can be attributed to the additive effect of genes. Using 110 baboons (80 females, 30 males), we 1) characterize normal variation in midshaft geometry of the femur with regard to age and sex, and 2) determine the degree to which the residual variation is attributable to additive genetic effects. Cross-sectional area (CSA), minimum (I(MIN)) and maximum (I(MAX)) principal moments of inertia, and polar moment of inertia (J) were calculated from digitized images of transverse midshaft sections. Maximum likelihood-based variance decomposition methods were used to estimate the mean effects of age, sex, and genes. Together age and sex effects account for approximately 56% of the variance in each property. In each case the effect of female sex is negative and that of age is positive, although of a lower magnitude than the effect of female sex. Increased age is associated with decreased mean cross-sectional geometry measures in the oldest females. Residual h(2) values range from 0.36 to 0.50, reflecting genetic effects accounting for 15% to 23% of the total phenotypic variance in individual properties. This study establishes the potential of the baboon model for the identification of genes that regulate bone geometric properties in primates. This model is particularly valuable because it allows for experimental designs, environmental consistency, availability of tissues, and comprehensive assessments of multiple integrated bone phenotypes that are not possible in human populations. The baboon is of particular importance in genetic studies, because it provides results that are likely highly relevant to the human condition due to the phylogenetic proximity of baboons to humans.

LRP5 sequence and polymorphisms in the baboon.

BACKGROUND: LRP5 is known to have an important relationship with bone density and a variety of other biological processes. Mapping to human chromosome 11q13.2, LRP5 shows considerable evolutionary conservation. Orthologs of this gene exist in many species, although comparison of human LRP5 with other non-human primates has not been performed until now. METHODS: We reported the complementary DNA (cDNA) sequence and deduced amino acid sequence for baboon LRP5, and compared the baboon and human sequences. cDNA sequences for 21 baboons were examined to identify single-nucleotide polymorphisms (SNPs). RESULTS: Sequences of coding regions in human and baboon LRP5 showed 97- 99% homology. Twenty-five SNPs were identified in the coding region of baboon LRP5. CONCLUSION: The observed degree of coding sequence homology in LRP5 led us to expect that the baboon may serve as a useful model for future research into the role(s) of this gene in primate metabolic diseases.

Spatial variation in osteonal bone properties relative to tissue and animal age.

Little is known about osteonal bone mineral and matrix properties, although these properties are of major importance for the understanding of bone alterations related to age and bone diseases such as osteoporosis. During aging, bone undergoes modifications that compromise their structural integrity as shown clinically by the increase of fracture incidence with age. Based on Fourier transform infrared (FTIR) analysis from baboons between 0 and 32 yr of age, consistent systematic variations in bone properties as a function of tissue age are reported within osteons. The patterns observed were independent of animal age and positively correlated with bone tissue elastic behavior measured by nano-indentation. As long as tissue age is expressed as a percentage of the entire osteon radius, osteonal analyses can be used to characterize disease changes independent of the size of the osteon. These mineral and matrix analyses can be used to explain bone fragility. The mineral content (mineral-to-matrix ratio) was correlated with the animal age in both old (interstitial) and newly formed bone tissue, showing for the first time that age-related changes in BMC can be explain by an alteration in the mineralization process itself and not only by an imbalance in the remodeling process.

A genomewide linkage scan for quantitative trait loci influencing the craniofacial complex in baboons (Papio hamadryas spp.).

Numerous studies have detected significant contributions of genes to variation in development, size, and shape of craniofacial traits in a number of vertebrate taxa. This study examines 43 quantitative traits derived from lateral cephalographs of 830 baboons (Papio hamadryas) from the pedigreed population housed at the Southwest National Primate Research Center. Quantitative genetic analyses were conducted using the SOLAR analytic platform, a maximum-likelihood variance components method that incorporates all familial information for parameter estimation. Heritability estimates were significant and of moderate to high magnitude for all craniofacial traits. Additionally, 14 significant quantitative trait loci (QTL) were identified for 12 traits from the three developmental components (basicranium, splanchnocranium, and neurocranium) of the craniofacial complex. These QTL were found on baboon chromosomes (and human orthologs) PHA1 (HSA1), PHA 2 (HSA3), PHA4 (HSA6), PHA11 (HSA12), PHA13 (HSA2), PHA16 (HSA17), and PHA17 (HSA13) (PHA, P. hamadryas; HSA, Homo sapiens). This study of the genetic architecture of the craniofacial complex in baboons provides the groundwork needed to establish the baboon as an animal model for the study of genetic and nongenetic influences on craniofacial variation.

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

UNLABELLED: Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. INTRODUCTION: Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. MATERIALS AND METHODS: Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. RESULTS: Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p

Inheritance of sutural pattern at the pterion in Rhesus monkey skulls.

Five of the bones that characteristically comprise the cranial vault articulate on the lateral aspect of the skull at or near the cephalometric landmark referred to as the pterion. The pattern of articulation in the sutures associated with these bones varies among and within primate species and has been used as a criterion for classification in taxonomic studies, as well as in archeological and forensic studies. Within species, the sutural patterns found within the region of the pterion have remarkable consistency, which lead to the hypothesis that these patterns have a genetic basis. Sutural pattern variations were investigated at the pterion in 422 skulls from 66 rhesus monkey families with known genealogies from the long-standing colony on Cayo Santiago. Four specific types of articulation patterns were recorded. The results demonstrated that the most common suture pattern at the pterion of Cayo Santiago rhesus monkeys (86%; similar to that seen in some other anthropoid species but not humans and some apes) was characterized by an articulation between the temporal bone and parietal bone. Articulation between the sphenoid and parietal bones (type SP) accounted for 14% of the specimens and was concentrated in a dozen families. Mothers with the SP phenotype had a high incidence of offspring with SP phenotypes. Most non-SP mothers having SP offspring had siblings or family members from previous generations with the SP type. This is the first study to examine variation in sutural patterns at the pterion in pedigrees. Variation of sutural patterns shows familial aggregation, suggesting that this variation is heritable. Future work will be focused on defining the inheritance patterns of variation at the pterion, with the ultimate objective of identifying the specific genes involved and their mechanism of action.

QTL with pleiotropic effects on serum levels of bone-specific alkaline phosphatase and osteocalcin maps to the baboon ortholog of human chromosome 6p23-21.3.

UNLABELLED: Bone ALP and OC are under partial genetic control. This study of 591 pedigreed baboons shows a QTL corresponding to human 6p23-21.3 that accounts for 25% (bone ALP) and 20% (OC) of the genetic variance. A gene affecting osteoblast activity, number, or recruitment likely resides in this area. INTRODUCTION: Serum levels of bone alkaline phosphatase (ALP) and osteocalcin (OC) reflect osteoblast activity. Both of these measures are under partial genetic control. Genetic effects on bone ALP have not been previously localized to chromosomal regions in primates, nor has the degree to which genetic effects are shared (pleiotropic) between bone ALP and OC been studied. MATERIALS AND METHODS: We applied variance components methods to a sample of 591 adult pedigreed baboons to detect and quantify effects of genes that influence bone ALP and that have pleiotropic effects on bone ALP and OC. A univariate linkage analysis was conducted for bone ALP. Bivariate linkage analyses were conducted in areas for which the bone ALP results presented here and a previous univariate OC linkage analysis showed evidence for linkage on the same chromosome for both bone ALP and OC. RESULTS: A quantitative trait locus (QTL) for serum levels of bone ALP is evident on the baboon ortholog of human chromosomal region 6p (LOD 2.93). Thirty-seven percent (genetic correlation [rho(G)] = 0.61) of the genetic variance in bone ALP and OC is caused by pleiotropic effects of the same gene(s). Bivariate linkage analysis revealed a QTL in the region corresponding to human chromosome 6p23-21.3, with the strongest evidence for bivariate linkage near D6S422 (LOD = 2.97 at 22 cM from our pter-most marker). D6S422 maps to 20.4 Mb in the human genome. The QTL-specific heritability (h2) is 0.25 and 0.20 for bone ALP and OC, respectively. CONCLUSIONS: This first formal test for shared genetic effects on two serum markers of osteoblast activity indicates that a significant pleiotropic effect on bone ALP and OC levels, and thus on bone formation, is detectible. The fact that this region corresponds to one on mouse chromosome 13 that has repeatedly yielded QTLs for BMD should encourage more intensive study of the effect of genes in this region on bone maintenance and turnover.

Association mapping: methodologies, strategies, and issues.

Recent advances in molecular genetic technology allow for detailed characterization of genetic variation and easy cost-efficient accumulation of such data, even for large human samples. One such advance that presents incredible opportunities for identifying associations between genetic polymorphisms and disease-related phenotypes is the ability to quickly type a large number of single-nucleotide polymorphisms (SNPs). Contributors to Group 10 of Genetic Analysis Workshop 14 explored the potential of SNP genotypes for the association mapping of disease-related genes in family-based studies. Using both real data involving alcoholism susceptibility, made available by the Collaborative Study on the Genetics of Alcoholism (COGA), and simulated data involving personality-disorder susceptibility, group members investigated specific methodological issues involved in association mapping, such as multiple testing, single SNPs vs. combinations and haplotypes, and the effect of linkage disequilibrium on SNP-based linkage; evaluated existing methodologies for association mapping using SNPs, short-tandem repeats (STRs), or a combination of the two; and introduced new or modified association-mapping methods, including a gamma random effects (GRE) model and the quantitative trait linkage disequilibrium (QTLD) test. These papers are unified by the application of association-based methods to analyze SNPs, microsatellite markers, or both, to identify chromosomal regions harboring genes that contribute to quantitative endophenotype variation, and thus to disease risk. Their diversity attests to the breadth and flexibility of association-mapping approaches to the genetics of complex disease.

Ontogeny of hematological cell and biochemical profiles in maternal and fetal baboons (Papio species).

The normal ranges of hematological cell profiles and biochemistry are documented in adult non-pregnant, pregnant, juvenile, and neonatal baboons. Despite the extensive use of the baboon as a model for the study of various aspects of pregnancy, there is no data from paired mothers and their fetuses at different stages of gestation. Hematologic and biochemical profile data were obtained from eight non-pregnant female baboons, 37 mothers and 38 fetal baboons at 30 +/- 2, 90 +/- 2, 125 +/- 2, and 175 +/- 2 days of gestation (mean +/- range; dGA; term, 180 dGA). Changes observed in fetal and maternal blood during normal baboon pregnancy were similar to those reported in human pregnancy. The level of alkaline phosphatase was two times higher in fetal blood circulation than that reported in human pregnancy.

The quantitative trait linkage disequilibrium test: a more powerful alternative to the quantitative transmission disequilibrium test for use in the absence of population stratification.

Linkage analysis based on identity-by-descent allele-sharing can be used to identify a chromosomal region harboring a quantitative trait locus (QTL), but lacks the resolution required for gene identification. Consequently, linkage disequilibrium (association) analysis is often employed for fine-mapping. Variance-components based combined linkage and association analysis for quantitative traits in sib pairs, in which association is modeled as a mean effect and linkage is modeled in the covariance structure has been extended to general pedigrees (quantitative transmission disequilibrium test, QTDT). The QTDT approach accommodates data not only from parents and siblings, but also from all available relatives. QTDT is also robust to population stratification. However, when population stratification is absent, it is possible to utilize even more information, namely the additional information contained in the founder genotypes. In this paper, we introduce a simple modification of the allelic transmission scoring method used in the QTDT that results in a more powerful test of linkage disequilibrium, but is only applicable in the absence of population stratification. This test, the quantitative trait linkage disequilibrium (QTLD) test, has been incorporated into a new procedure in the statistical genetics computer package SOLAR. We apply this procedure in a linkage/association analysis of an electrophysiological measurement previously shown to be related to alcoholism. We also demonstrate by simulation the increase in power obtained with the QTLD test, relative to the QTDT, when a true association exists between a marker and a QTL.

Genetic and environmental influences on thyroid hormone variation in Mexican Americans.

Thyroid hormones play major roles in the regulation of a wide range of metabolic and physiologic processes, but the genes and environmental factors that affect normal, quantitative variation in thyroid hormone concentrations are largely unknown. Using quantitative genetic methods, we evaluated the effects of genes and environmental factors on thyroid hormone variation in 586 women and 425 men from 27 randomly ascertained Mexican-American families from the San Antonio Family Heart Study. Data were available on free and total T(4), free and total T(3), TSH, thyroglobulin, and T(4)-binding globulin, as well as on covariates, including sex, age, weight, lifestyle habits, physical activity, and others. These covariates accounted for 2-18% of total phenotypic variation, whereas genes accounted for 26-64% of the variation. Overall, free T(3) had the highest heritability, which is noteworthy because it is the most biologically active thyroid hormone and accounts for the vast majority of metabolic and physiologic effects of thyroid hormones. Our results indicate that genes account for a substantial portion of variation in human thyroid hormone levels, and suggest that further studies to identify the genes involved in this variation could reveal important insights into the processes that govern thyroid-mediated metabolism.

Osteon remodeling dynamics in the Cayo Santiago Macaca mulatta: The effect of matriline.

At the microstructural level, bones remodel throughout life. This process is recorded in bone cortex as osteons. A more comprehensive understanding of the interaction between genetic regulation and environmental factors in osteon remodeling will increase the value of this skeletal record and enable more accurate reconstruction of individual life histories. The purpose of this study was to examine the contribution of maternal lineage to normal age and sex variation in osteon remodeling dynamics in Macaca mulatta. Femoral cross sections from 57 Cayo Santiago-derived rhesus macaques representing five matrilines were examined to evaluate the effect of genetic relatedness on osteon remodeling dynamics. Analysis of variance revealed an effect of maternal lineage on osteon area and Haversian canal area. The other variables did not differ significantly among matrilines. Analysis of covariance revealed no significant interactions among age, sex, and matriline for any of the microstructural variables.