Physical inactivity and knee osteoarthritis in guinea pigs.

OBJECTIVE: To investigate whether and how a sedentary lifestyle contributes to knee osteoarthritis (OA) incidence and severity. DESIGN: An experiment was conducted using Hartley guinea pigs, an established idiopathic knee OA model. To simulate a sedentary lifestyle, growing animals (n = 18) were housed for 22 weeks in small cages that restricted their mobility, while another group of animals (n = 17) received daily treadmill exercise to simulate moderate physical activity. After the experiment, histological assessments, biochemical assays, and mechanical testing were conducted to compare tibial articular cartilage structure, strength, and degree of OA degeneration between sedentary and physically active animals. Groups were also compared based on body weight and composition, as well as gut microbial community composition assessed using fecal 16S rRNA gene sequencing. RESULTS: Prevalence of knee OA was similar between sedentary and physically active animals, but severity of the disease (cartilage lesion depth) was substantially greater in the sedentary group (P = 0.02). In addition, during the experiment, sedentary animals developed cartilage with lower aggrecan quantity (P = 0.03) and accumulated more body weight (P = 0.005) and visceral adiposity (P = 0.007). Groups did not differ greatly, however, in terms of cartilage thickness, collagen quantity, or stiffness, nor in terms of muscle weight, subcutaneous adiposity, or gut microbial community composition. CONCLUSIONS: Our findings indicate that a sedentary lifestyle promotes the development of knee OA, particularly by enhancing disease severity rather than risk of onset, and this potentially occurs through multiple pathways including by engendering growth of functionally deficient joint tissues and the accumulation of excess body weight and adiposity.

A constitutive description of the anisotropic response of the fascia lata.

In this paper we propose a constitutive model to analyze in-plane extension of goat fascia lata. We first perform a histological analysis of the fascia that shows a well-organized bi-layered arrangement of undulated collagen fascicles oriented along two well defined directions. To develop a model consistent with the tissue structure we identify the absolute and relative thickness of each layer and the orientation of the preferred directions. New data are presented showing the mechanical response in uniaxial and planar biaxial extension. The paper proposes a constitutive relation to describe the mechanical response. We provide a summary of the main ingredients of the nonlinear theory of elasticity and introduce a suitable strain-energy function to describe the anisotropic response of the fascia. We validate the model by showing good fit of the numerical results and the experimental data. Comments are included about differences and analogies between goat fascia lata and the human iliotibial band.

Dietary consistency and the midline sutures in growing pigs.

OBJECTIVES: The purpose of this study was to investigate the effects of reduced masticatory function on midline suture growth and morphology in growing pigs. SETTING AND SAMPLE POPULATION: The sample was 20 pigs separated into two dietary groups and raised at the Department of Anthropology, Harvard University. Midline suture specimens were analyzed at the Department of Orthodontics, University of Washington. MATERIALS AND METHODS: Ten farm pigs and 10 minipigs, all male, were randomly assigned to hard (n = 9) and soft-diet (n = 11) groups. Fluorochromic mineral labels were administered to document bone apposition, and the animals were killed after 12 weeks. Undecalcified sections of the interfrontal, interparietal, internasal, and intermaxillary sutures were evaluated for bone quantity and sutural thickness, interdigitation ratio and growth rate. RESULTS: Soft-diet pigs were characterized by a slower rate of weight gain and less bone than their hard-diet counterparts. Even after correction for weight gain, soft-diet pigs had reduced suture growth rate and thickness. However, no difference in interdigitation ratio was detected between dietary groups. CONCLUSIONS: Restriction to a soft diet reduces midline suture growth and bone apposition in the growing pig.

Peripubertal estrogen levels and physical activity affect femur geometry in young adult women.

UNLABELLED: The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. INTRODUCTION: It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. METHODS: We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. RESULTS: At age 17, subjects with the highest E2 levels in year 1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. CONCLUSIONS: This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.

Control of jaw movements in two species of macropodines (Macropus eugenii and Macropus rufus).

The masticatory motor patterns of three tammar wallabies and two red kangaroos were determined by analyzing the pattern of electromyographic (EMG) activity of the jaw adductors and correlating it with lower jaw movements, as recorded by digital video and videoradiography. Transverse jaw movements were limited by the width of the upper incisal arcade. Molars engaged in food breakdown during two distinct occlusal phases characterized by abrupt changes in the direction of working-side hemimandible movement. Separate orthal (Phase I) and transverse (Phase II) trajectories were observed. The working-side lower jaw initially was drawn laterally by the balancing-side medial pterygoid and then orthally by overlapping activity in the balancing- and working-side temporalis and the balancing-side superficial masseter and medial pterygoid. Transverse movement occurred principally via the working-side medial pterygoid and superficial masseter. This pattern contrasted to that of placental herbivores, which are known to break down food when they move the working-side lower jaw transversely along a relatively longer linear path without changing direction during the power stroke. The placental trajectory results from overlapping activity in the working- and balancing-side adductor muscles, suggesting that macropods and placental herbivores have modified the primitive masticatory motor pattern in different ways.

Epigenetic interactions and the structure of phenotypic variation in the cranium.

Understanding the developmental and genetic basis for evolutionarily significant morphological variation in complex phenotypes such as the mammalian skull is a challenge because of the sheer complexity of the factors involved. We hypothesize that even in this complex system, the expression of phenotypic variation is structured by the interaction of a few key developmental processes. To test this hypothesis, we created a highly variable sample of crania using four mouse mutants and their wild-type controls from similar genetic backgrounds with developmental perturbations to particular cranial regions. Using geometric morphometric methods we compared patterns of size, shape, and integration in the sample within and between the basicranium, neurocranium, and face. The results highlight regular and predictable patterns of covariation among regions of the skull that presumably reflect the epigenetic influences of the genetic perturbations in the sample. Covariation between relative widths of adjoining regions is the most dominant factor, but there are other significant axes of covariation such as the relationship between neurocranial size and basicranial flexion. Although there are other sources of variation related to developmental perturbations not analyzed in this study, the patterns of covariation created by the epigenetic interactions evident in this sample may underlie larger scale evolutionary patterns in mammalian craniofacial form.

Trabecular bone in the bird knee responds with high sensitivity to changes in load orientation.

Wolff's law of trajectorial orientation proposes that trabecular struts align with the orientation of dominant compressive loads within a joint. Although widely considered in skeletal biology, Wolff's law has never been experimentally tested while controlling for ontogenetic stage, activity level, and species differences, all factors that may affect trabecular bone growth. Here we report an experimental test of Wolff's law using a within-species design in age-matched subjects experiencing physiologically normal levels of bone strain. Two age-matched groups of juvenile guinea fowl Numida meleagris ran on a treadmill set at either 0 degrees (Level group) or 20 degrees (Incline group), for 10 min per day over a 45-day treatment period. Birds running on the 20 degrees inclined treadmill used more-flexed knees than those in the Level group at midstance (the point of peak ground reaction force). This difference in joint posture enabled us to test the sensitivity of trabecular alignment to altered load orientation in the knee. Using a new radon transform-based method for measuring trabecular orientation, our analysis shows that the fine trabecular bone in the distal femur has a high degree of correspondence between changes in joint angle and trabecular orientation. The sensitivity of this response supports the prediction that trabecular bone adapts dynamically to the orientation of peak compressive forces.

Articular area responses to mechanical loading: effects of exercise, age, and skeletal location.

How reliable are reconstructions of body mass and joint function based on articular surface areas? While the dynamic relationship between mechanical loading and cross-sectional geometry in long bones is well-established, the effect of loading on the subchondral articular surface area of epiphyses (hereafter, articular surface area, or ASA) has not been experimentally tested. The degree to which ASA can change in size and shape is important, because articular dimensions are frequently used to estimate body mass and positional behavior in fossil species. This study tests the hypothesis that mechanical loading influences ASA by comparing epiphyses of exercised and sedentary sheep from three age categories: juvenile, subadult, and adult (n = 44). ASA was measured on latex molds of subchondral articular surfaces of 10 epiphyses from each sheep. Areas were standardized by body mass, and compared to diaphyseal cross-sectional geometrical data. Nonparametric statistical comparisons of exercised and control individuals found no increases in ASA in response to mechanical loading in any age group. In contrast, significant differences in diaphyseal cross-sectional geometry were detected between exercised and control groups, but mostly in juveniles. The conservatism of ASA supports the hypothesis that ASA is ontogenetically constrained, and related to locomotor behavior at the species level and to body mass at the individual level, while variations in diaphyseal cross-sectional geometry are more appropriate proxies for individual variations in activity level.

Posterior maxillary (PM) plane and anterior cranial architecture in primates.

This study tests several hypotheses of integration between the cranial base and face in primates. After reviewing the definition and anatomical basis for the posterior maxillary (PM) plane, which demarcates the back of the midface at its junction with the sphenoid, we demonstrate how the PM plane can be identified accurately on radiographs, and confirm that it maintains a 90 degrees angle relative to the Neutral Horizontal Axis of the orbits in all primates. In addition, we use the PM plane to test Dabelow's (1929) hypothesis that the orbits and anterior cranial base are more highly integrated in anthropoids than in strepsirrhines, and we test the hypothesis that the midline anterior cranial base (planum sphenoideum) and anterior cranial floor (planum sphenoideum plus cribriform plate) in primates are highly correlated with each other relative to the PM plane. The mean angle between the anterior cranial base and the PM plane does not differ significantly from 90 degrees in anthropoids, but differs significantly in strepsirrhines. The anterior cranial base and anterior cranial floor, however, correlate well with each other relative to the PM plane in both suborders of primates, independent of orbital orientation and configuration. The PM plane, anterior cranial base, and anterior cranial floor, therefore, form an integrated structural complex, a "facial block," whose orientation relative to the posterior cranial base influences craniofacial shape among anthropoids in which orbital orientation influences the orientation of the anterior cranial base. One such effect is that increases in cranial base flexion shorten the antero-posterior length of the nasopharynx.

Craniodental variation in Paranthropus boisei: a developmental and functional perspective.

What levels and patterns of craniodental variation among a fossil hypodigm are necessary to reject the null hypothesis that only a single species is sampled? We suggest how developmental and functional criteria can be used to predict where in the skeleton of fossil hominins we should expect more, or less, within-species variation. We present and test three hypotheses about the factors contributing to craniodental variation in extant primate taxa, and then apply these results to the interpretation of the P. boisei hypodigm. Within the comparative samples of extant Homo, Pan, Gorilla, Pongo, and Colobus, variables from the cranial base, neurocranium, and face that are not subject to high magnitudes of strain have consistently lower levels of intraspecific variation than variables from regions of the face subject to high levels of strain. Dental size variables are intermediate in terms of their reliability. P. boisei is found to have a low degree of variability relative to extant primates for variables shown to be generally useful for testing taxonomic hypotheses. Contrary to the claims of Suwa et al. ([1997] Nature 389:489-492), the recently discovered material from Konso falls within the range of variation of the "pre-Konso" hypodigm of P. boisei for available conventional metrical variables. Those aspects of the Konso material that appear to extend the range of the P. boisei hypodigm involve regions of the skull predicted to be prone to high levels of within-species variation. The approach used in this study focuses on craniodental data, but it is applicable to other regions of the skeleton.

Ontogeny of postnatal hyoid and larynx descent in humans.

Postnatal descent of the hyoid and larynx relative to the palate and mandible, which occurs uniquely in humans, is an anatomical prerequisite for quantal speech. This study tested the hypothesis that spatial constraints related to deglutition impose greater restrictions on the rate and degree of hyo-laryngeal descent than do adaptations for vocalization. Ontogenetic data on changes in the size and shape of the pharynx, the vocal tract, and the spatial positions of the larynx, hyoid, mandible and hard palate relative to each other and to the oral cavity were obtained for 15 males and 13 females from a longitudinal series of lateral radiographs (the Denver Growth Study) taken between the ages of 1 month and 14 years. To establish growth patterns, nine linear dimensions of the pharynx and 15 different pharyngeal and vocal-tract proportions were regressed against percentage growth. The results demonstrate that certain aspects of vocal-tract shape change markedly during ontogeny, especially in the first postnatal year and during the adolescent growth spurt. The ratio of pharynx height to oral cavity length (which is important for speech) decreases significantly (P<0.001) from 1.5 to 1.0 between birth and 6-8 years, after which it remains stable. In contrast, regression analyses indicated that superoinferior spatial relations between the positions of the vocal folds, the hyoid body, the mandible and the hard palate do not change significantly throughout the entire postnatal growth period (P<0.05). Sexual dimorphism in pharyngeal shape and size before the age of 14 years is very limited. The results suggest that the descent of the hyoid and larynx relative to the mandible is constrained by muscle function related to deglutition, highlighting the different functional roles of the hyoid during speech and oral transport.

The primate cranial base: ontogeny, function, and integration.

Understanding the complexities of cranial base development, function, and architecture is important for testing hypotheses about many aspects of craniofacial variation and evolution. We summarize key aspects of cranial base growth and development in primates that are useful for formulating and testing hypotheses about the roles of the chondrocranium and basicranium in cranial growth, integration, and function in primate and human evolution. We review interspecific, experimental, and ontogenetic evidence for interactions between the cranial base and brain, and between the cranial base and the face. These interactions indicate that the cranial base plays a key role in craniofacial growth, helping to integrate, spatially and functionally, different patterns of growth in various adjoining regions of the skull such as components of the brain, the eyes, the nasal cavity, the oral cavity, and the pharynx. Brain size relative to cranial base length appears to be the dominant influence on many aspects of basicranial variation, especially the angle of the cranial base in the midsagittal plane, but other factors such as facial size, facial orientation, and posture may also be important. Major changes in cranial base shape appear to have played crucial roles in the evolution of early primates, the origin of anthropoids, and the origin of Homo sapiens.

Why fuse the mandibular symphysis? A comparative analysis.

Fused symphyses, which evolved independently in several mammalian taxa, including anthropoids, are stiffer and stronger than unfused symphyses. This paper tests the hypothesis that orientations of tooth movements during occlusion are the primary basis for variations in symphyseal fusion. Mammals whose teeth have primarily dorsally oriented occlusal trajectories and/or rotate their mandibles during occlusion will not benefit from symphyseal fusion because it prevents independent mandibular movements and because unfused symphyses transfer dorsally oriented forces with equal efficiency; mammals with predominantly transverse power strokes are predicted to benefit from symphyseal fusion or greatly restricted mediolateral movement at the symphysis in order to increase force transfer efficiency across the symphysis in the transverse plane. These hypotheses are tested with comparative data on symphyseal and occlusal morphology in several mammals, and with kinematic and EMG analyses of mastication in opossums (Didelphis virginiana) and goats (Capra hircus) that are compared with published data on chewing in primates. Among mammals, symphyseal fusion or a morphology that greatly restricts movement correlates significantly with occlusal orientation: species with more transversely oriented occlusal planes tend to have fused symphyses. The ratio of working- to balancing-side adductor muscle force in goats and opossums is close to 1:1, as in macaques, but goats and opossums have mandibles that rotate independently during occlusion, and have predominantly vertically oriented tooth movements during the power stroke. Symphyseal fusion is therefore most likely an adaptation for increasing the efficiency of transfer of transversely oriented occlusal forces in mammals whose mandibles do not rotate independently during the power stroke.

Basicranial influence on overall cranial shape.

This study examines the extent to which the major dimensions of the cranial base (maximum length, maximum breadth, and flexion) interact with brain volume to influence major proportions of the neurocranium and face. A model is presented for developmental interactions that occur during ontogeny between the brain and the cranial base and neurocranium, and between the neurobasicranial complex (NBC) and the face. The model is tested using exocranial and radiographic measurements of adult crania sampled from five geographically and craniometrically diverse populations. The results indicate that while variations in the breadth, length and flexion of the cranial base are mutually independent, only the maximum breadth of the cranial base (POB) has significant effects on overall cranial proportions, largely through its interactions with brain volume which influence NBC breadth. These interactions also have a slight influence on facial shape because NBC width constrains facial width, and because narrow-faced individuals tend to have antero-posteriorly longer faces relative to facial breadth than wide-faced individuals. Finally, the model highlights how integration between the cranial base and the brain may help to account for the developmental basis of some morphological variations such as occipital bunning. Among modern humans, the degree of posterior projection of the occipital bone appears to be a consequence of having a large brain on a relatively narrow cranial base. Occipital buns in Neanderthals, who have wide cranial bases relative to endocranial volume, may not be entirely homologous with the morphology occasionally evident in Homo sapiens.

The ontogeny of cranial base angulation in humans and chimpanzees and its implications for reconstructing pharyngeal dimensions.

This paper examines differences in the processes by which the cranial base flexes in humans and extends in chimpanzees. In addition, we test the extent to which one can use comparisons of cranial base angles in humans and non-human primates to predict vocal tract dimensions. Four internal cranial base angles and one external cranial base angle were measured in a longitudinal sample of Homo sapiens and a cross-sectional sample of Pan troglodytes. These data show that the processes of cranial base angulation differ substantially in these species. While the human cranial base flexes postnatally in a rapid growth trajectory that is complete by two years, the cranial base in P. troglodytes extends postnatally in a more prolonged skeletal growth trajectory. These comparisons also demonstrate that the rate of cranial base angulation is comparable for different measures, but that angles which incorporate different anterior cranial base measurements correlate poorly. We also examined ontogenetic relationships between internal and external cranial base angles and vocal tract growth in humans to test the hypothesis that cranial base angulation influences pharyngeal dimensions and can, therefore, be used to estimate vocal tract proportions in fossil hominids. Our results indicate that internal and external cranial base angles are independent of the horizontal and vertical dimensions of the vocal tract. Instead, a combination of mandibular and palatal landmarks can be used to predict dimensions of the vocal tract in H. sapiens. The developmental contrasts in cranial base angulation between humans and non-human primates may have important implications for testing hypotheses about the relationship between cranial base flexion and other craniofacial dimensions in hominid evolution.

Sphenoid shortening and the evolution of modern human cranial shape.

Crania of 'anatomically modern' Homo sapiens from the Holocene and Upper Pleistocene epochs differ from those of other Homo taxa, including Neanderthals, by only a few features. These include a globular braincase, a vertical forehead, a dimunitive browridge, a canine fossa and a pronounced chin. Humans are also unique among mammals in lacking facial projection: the face of the adult H. sapiens lies almost entirely beneath the anterior cranial fossa, whereas the face in all other adult mammals, including Neanderthals, projects to some extent in front of the braincase. Here I use radiographs and computed tomography to show that many of these unique human features stem partly from a single, ontogenetically early reduction in the length of the sphenoid, the central bone of the cranial base from which the face grows forward. Sphenoid reduction, through its effects on facial projection and cranial shape, may account for the apparently rapid evolution of modern human cranial form, and suggests that Neanderthals and other archaic Homo should be excluded from H. sapiens.

How and why humans grow thin skulls: experimental evidence for systemic cortical robusticity.

To what extent is cranial vault thickness (CVT) a character that is strongly linked to the genome, or to what extent does it reflect the activity of an individual prior to skeletal maturity? Experimental data from pigs and armadillos indicate that CVT increases more rapidly in exercised juveniles than in genetically similar controls, despite the low levels of strain generated by chewing or locomotion in the neurocranium. CVT increases in these individuals appear to be a consequence of systemic cortical bone growth induced by exercise. In addition, an analysis of the variability in vault thickness in the genus Homo demonstrates that, until the Holocene, there has been only a slight, general decrease in vault thickness over time with no consistent significant differences between archaic and early anatomically modern humans from the Late Pleistocene. Although there may be some genetic component to variation in CVT, exercise-related, non-genetically heritable stimuli appear to account for most of the variance between individuals. The thick cranial vaults of most hunter-gatherers and early agriculturalists suggests that they may have experienced higher levels of sustained exercise relative to body mass than the majority of recent, post-industrial humans.

Life history variables preserved in dental cementum microstructure.

The age and season of death of mammals, as well as other aspects of their life history, can be estimated from seasonal bands in dental cementum that result from variations in microstructure. Scanning electron micrographs of goats fed controlled diets demonstrate that cementum bands preserve variations in the relative orientation of collagen fibers that reflect changes in the magnitude and frequency of occlusal forces from chewing different quality diets. Changes in the rate of tissue growth are also reflected in cementum bands as variations in the degree of mineralization.