Bone Functional Adaptation Research Articles

Internal architecture of the mandibular condyle of rabbits is related to dietary resistance during growth.

Although there is considerable evidence that bone responds to the loading environment in which it develops, few analyses have examined phenotypic plasticity or bone functional adaptation in the masticatory apparatus. Prior work suggests that masticatory morphology is sensitive to differences in food mechanical properties during development; however, the importance of the timing/duration of loading and variation in naturalistic diets is less clear. Here, we examined microstructural and macrostructural differences in the mandibular condyle in four groups of white rabbits (Oryctolagus cuniculus) raised for a year on diets that varied in mechanical properties and timing of the introduction of mechanically challenging foods, simulating seasonal variation in diet. We employed sliding semilandmarks to locate multiple volumes of interest deep to the mandibular condyle articular surface, and compared bone volume fraction, trabecular thickness and spacing, and condylar size/shape among experimental groups. The results reveal a shared pattern of bony architecture across the articular surface of all treatment groups, while also demonstrating significant among-group differences. Rabbits raised on mechanically challenging diets have significantly increased bone volume fraction relative to controls fed a less challenging diet. The post-weaning timing of the introduction of mechanically challenging foods also influences architectural properties, suggesting that bone plasticity can extend well into adulthood and that bony responses to changes in loading may be rapid. These findings demonstrate that bony architecture of the mandibular condyle in rabbits responds to variation in mechanical loading during an organism's lifetime and has the potential to track dietary variation within and among species.

Footedness related differences in femoral bone mineral density in elderly women with osteoporosis

Purpose: The presumed link between lateralized habitual motor activity and bilateral skeletal asymmetry, as result of bone functional adaptation, is the basis for inferences about bone mineral distribution; consequently, bone loss and osteoporosis. As there is no research connecting directly footedness with osteoporosis, the present study was designed to investigate their relation, in elderly women with osteoporosis.Methods: A sample of 420 white, Caucasian race women, older than 65 years, with previous diagnosis of osteoporosis, was recruited for the study. Finally, 164 women met the inclusion criteria and participated. The femoral neck and total hip bone mineral density (BMD) differences between right and left hips of 105 right-footed and 59 non-right-footed women, and the between footedness groups differences of the above right-left BMD differences, were measured with Dual-energy X-ray Absorptiometry (DXA).Results: In right-footers, total hip right-left BMD differences were statistically significant, favoring left femur [t(104) = –2.79, p < .01, two tailed]. In non-right-footers, femoral neck right-left BMD differences were statistically significant, favoring right femur [t(58) =2.025, p < .05, two tailed]. Femoral neck and total hip right-left BMD differences of right- versus non-right-footed women were statistically insignificant.Conclusion: The dominance of the right lower limb had an asymmetric effect on left total hip BMD, while non-right-footedness favored right femoral neck BMD. The findings highlighted the influence of load bearing effects of the body weight and muscle contractions on femoral BMD. We noted a possible association between footedness and BMD, as a result of bone functional adaptation.

Are we crying Wolff? 3D printed replicas of trabecular bone structure demonstrate higher stiffness and strength during off-axis loading.

Roux's principle of bone functional adaptation postulates that bone tissue, and particularly trabecular bone tissue, responds to mechanical stimuli by adjusting (modeling) its architecture accordingly. Hence, it predicts that the new modeled trabecular structure is mechanically improved (stiffer and stronger) in line with the habitual in vivo loading direction. While previous studies found indirect evidence to support this theory, direct support was so far unattainable. This is attributed to the fact that each trabecular bone is unique, and that trabecular bone tissue tends to be damaged during mechanical testing. Consequently, a unique modeled trabecular structure can be mechanically tested only along one direction and a comparison to other directions for that specific structure is impossible. To address this issue, we have 3D printed 10 replicas of a trabecular structure from a sheep talus cropped along the 3 principal axes of the bone and in line with the principal direction of loading (denoted on-axis model). Next, we have rotated the same cropped trabecular structure in increments of 10° up to 90° to the bone principal direction of loading (denoted off-axis models) and printed 10 replicas of each off-axis model. Finally, all on-axis and off-axis 3D printed replicas were loaded in compression until failure and trabecular structure stiffness and strength were calculated. Contrary to our prediction, and conflicting with Roux's principle of bone functional adaptation, we found that a trabecular structure loaded off-axis tended to have higher stiffness and strength values when compared to the same trabecular structure loaded on-axis. These unexpected results may not disprove Roux's principle of bone functional adaptation, but they do imply that trabecular bone adaptation may serve additional purposes than simply optimizing bone structure to one principal loading scenario and this suggests that we still don't fully understand bone modeling in its entirety.

Trabecular architecture in the humeral metaphyses of non-avian reptiles (Crocodylia, Squamata and Testudines): Lifestyle, allometry and phylogeny.

The lifestyle of extinct tetrapods is often difficult to assess when clear morphological adaptations such as swimming paddles are absent. According to the hypothesis of bone functional adaptation, the architecture of trabecular bone adapts sensitively to physiological loadings. Previous studies have already shown a clear relation between trabecular architecture and locomotor behavior, mainly in mammals and birds. However, a link between trabecular architecture and lifestyle has rarely been examined. Here, we analyzed trabecular architecture of different clades of reptiles characterized by a wide range of lifestyles (aquatic, amphibious, generalist terrestrial, fossorial, and climbing). Humeri of squamates, turtles, and crocodylians have been scanned with microcomputed tomography. We selected spherical volumes of interest centered in the proximal metaphyses and measured trabecular spacing, thickness and number, degree of anisotropy, average branch length, bone volume fraction, bone surface density, and connectivity density. Only bone volume fraction showed a significant phylogenetic signal and its significant difference between squamates and other reptiles could be linked to their physiologies. We found negative allometric relationships for trabecular thickness and spacing, positive allometries for connectivity density and trabecular number and no dependence with size for degree of anisotropy and bone volume fraction. The different lifestyles are well separated in the morphological space using linear discriminant analyses, but a cross-validation procedure indicated a limited predictive ability of the model. The trabecular bone anisotropy has shown a gradient in turtles and in squamates: higher values in amphibious than terrestrial taxa. These allometric scalings, previously emphasized in mammals and birds, seem to be valid for all amniotes. Discriminant analysis has offered, to some extent, a distinction of lifestyles, which however remains difficult to strictly discriminate. Trabecular architecture seems to be a promising tool to infer lifestyle of extinct tetrapods, especially those involved in the terrestrialization.

Artificial Selection for Increased Voluntary Wheel Running Alters Limb Skeleton Shape and Exercise Plasticity in Mice

Individual skeletal morphology is determined by genetic effects and within‐generation phenotypic plasticity in response to mechanical loading. Changes in limb bone morphology associated with locomotor activity through ontogeny and across evolutionary time can provide insight into adaptation in locomotor systems. Here, we investigate the effects of long‐term selection for locomotor activity on the gross morphology and exercise response of the hind limb skeleton using a mouse model. A founding population of Hsd:ICR outbred mouse stock was divided into closed lines of “high runner” (HR) and control (C) animals. HR mice were bred for increased voluntary wheel‐running distance by breeding animals (n=10 pairs per generation) with the highest average wheel revolutions on days 5 and 6 of a 6‐day wheel exposure protocol. Control animals were also wheel‐tested but were randomly paired. Male HR and C mice from experimental generation 82 were randomly assigned at 5 weeks of age to be permitted or denied wheel access for 4 weeks, resulting in 4 experimental groups: C wheel (n=12), C no wheel (n=12), HR wheel (n=10), and HR no wheel (n= 10). Following wheel access, mice were euthanized and right hind limbs were micro‐CT scanned (~20 um voxel size). Three‐dimensional shapes of the os coxa, femur, and tibia were defined by digitizing 18, 23, and 18 landmarks, respectively, on each specimen. To adjust for size, individual bones were scaled to the geometric mean of all possible linear distances among landmarks. Between‐group differences were analyzed using canonical variates analysis (CVA) and localized using the Euclidean distance matrix analysis (EDMA) Form procedure. EDMA Growth procedure was used to compare the trajectories of exercise‐induced skeletal plasticity between HR and C animals. Differences ≥3% were considered substantial for both EDMA methods. Shape analyses revealed differences in morphological lability among the three limb bones examined and in subsections within each bone. More specifically, the mean hind limb skeletal morphology, especially of the pelvis and proximal femur, substantially differed between HR and C mice. Plastic bony responses to exercise also differed, most substantially in the iliac blade, ischial tuberosity, and proximal femur. Finally, throughout the hind limb, the baseline skeletal morphology of HR mice did not resemble the exercise response of C animals, indicating that genetic assimilation of plastic bone responses did not occur in this model. The results suggest regional sensitivity of the hind limb skeleton to plastic and evolved morphological change, provide further evidence of genetic influence on bone functional adaptation, and inform our understanding of the evolutionary lability of the musculoskeletal system over evolutionary timescales.Support or Funding InformationUniversity of Missouri School of Medicine, University of Missouri Dissertation Research Travel AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intensive terrestrial or marine locomotor strategies are associated with inter- and intra-limb bone functional adaptation in living female athletes.

ObjectivesTo systematically characterize intra‐limb patterns of skeletal plasticity to loading among living women, in order to better understand regional complexity in structural adaptation within the lower limb and more accurately infer behavior in the past.Materials and methodsWe used peripheral quantitative computed tomography imaging of the femur, tibia, first and second metatarsals to quantify bone morphology among female controls and athletes representative of either terrestrial or marine mobility, grouped by loading category (odd‐impact, repetitive low‐impact, and high‐magnitude). Parameters included midshaft bone density, areas, rigidity, and shape, epiphyseal bone densities and areas. We assessed between‐group differences and the influence of training history on significant variation among the loading groups.ResultsTerrestrial mobility strategies were best distinguished by significant midshaft periosteal hypertrophy across the lower limb/foot relative to controls, and by particularly high midshaft femoral and tibial cortical bone areas relative to rowers. Enhanced midshaft bone area was typically paired with decreased bone density among athlete groups. Sport‐specific variation in training duration/timing was significantly correlated with multiple midshaft parameters.DiscussionResults demonstrate characteristic patterns of intra‐limb adaptation to terrestrial and marine mobility strategies among active women relative to controls, and highlight components of these patterns that may be shaped in part by differences in loading duration/timing. Additionally, our findings support constraints on skeletal variation in the distal tibia and foot relative to more proximal locations about the knee among living women. For example, metatarsal variation was constrained, but where present reflected sport‐specific variation in force distribution in the foot.

Trabecular bone functional adaptation and sexual dimorphism in the human foot.

Trabecular bone adapts to the strains placed upon the skeleton during life. Anthropological research has largely focused on linking variation in primate trabecular bone to locomotor mode, to provide a context for interpreting fossil morphology. However, intraspecific variation and its underlying mechanisms are still poorly understood. Trabecular bone is influenced by a variety of factors including body mass, age, diet, temperature, genetics, sex, and behavior. Before trabecular structure can be used to infer habitual behavior in the past, the effects of these factors need to be understood. In this article, we examine variation in trabecular structure in the human foot in four archaeological groups in relation to inferred levels of terrestrial mobility and sex. We use high-resolution μCT scanning to examine variation in trabecular structure in the human calcaneus, talus, and first metatarsal in two relatively mobile and two relatively sedentary archaeological groups. The four population samples show similar patterns of trabecular variation throughout the foot, influenced by mechanical loading. Greater inferred terrestrial mobility is associated with greater bone volume fraction and thicker, more widely spaced, and less interconnected trabeculae. However, contrary to diaphyseal rigidity, only limited sexual dimorphism was found in trabecular structure. This work demonstrates that trabecular bone may serve as a useful proxy of habitual behavior in the fossil and archaeological record when other factors are carefully considered. However, the mechanisms underlying sexual dimorphism are not well understood. As such, inferring sex differences in habitual behavior is currently challenging.

Bone functional adaptation does not erase neutral evolutionary information.

To investigate whether diaphyseal and craniofacial variation similarly reflect neutral genetic variation among modern European and South Africans. Diaphyseal and craniofacial data were collected on English, South European, and South African samples. The Relethford-Blangero model was used to compare predicted among-population relationships generated by limb bones relative to those generated by the crania and, further, to test whether adaptive plasticity affected these predicted relationships. Evidence of adaptive plasticity was confirmed by comparing J, an indicator of limb bone robusticity, among individuals who worked different occupations in industrializing Lisbon (Portugal) and Bologna (Italy). Diaphyses were more variable than were crania and more robust in individuals with physically demanding occupations-both consistent with expectations of adaptive plasticity. However, diaphyseal variation still generated among-population relationships consistent with neutral genetic predictions and Mantel tests confirmed a high, significant correlation between diaphyseal and craniofacial distance matrices. This pattern was not strongly affected by adaptive plasticity. Among-population patterns of diaphyseal variation are consistent with neutral expectations and are consistent with historical data on population composition, genetics, and migration. Furthermore, plasticity induced by Industrial-era levels of physical activity does not erase these neutral signatures. Diaphyseal variation may therefore be useful to infer neutral (presumably genetic) information across populations, and controlling for existing relationships may strengthen inferences of physical activity made when comparing limb bone structure across populations.

Functional morphology in the pages of the AJPA

Functional morphology in the pages of the <i>AJPA</i>

Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR). However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK’s, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), c-jun, and c-fos in dorsal root ganglion (DRG) of the brachial intumescence were performed. There was a significant increase in signaling through MAPK’s including extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05). However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the molecular events involved in regulation of bone adaptation is needed to understand the timing and impact of loading events, and the contribution of the neuronal signaling to functional adaptation of bone.

Histomorphometry and cortical robusticity of the adult human femur.

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n=233) and female (n=217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

Trabecular bone in the calcaneus of runners.

Trabecular bone of the human calcaneus is subjected to extreme repetitive forces during endurance running and should adapt in response to this strain. To assess possible bone functional adaptation in the posterior region of the calcaneus, we recruited forefoot-striking runners (n = 6), rearfoot-striking runners (n = 6), and non-runners (n = 6), all males aged 20–41 for this institutionally approved study. Foot strike pattern was confirmed for each runner using a motion capture system. We obtained high resolution peripheral computed tomography scans of the posterior calcaneus for both runners and non-runners. No statistically significant differences were found between runners and nonrunners or forefoot strikers and rearfoot strikers. Mean trabecular thickness and mineral density were greatest in forefoot runners with strong effect sizes (<0.80). Trabecular thickness was positively correlated with weekly running distance (r2 = 0.417, p<0.05) and years running (r2 = 0.339, p<0.05) and negatively correlated with age at onset of running (r2 = 0.515, p<0.01) Trabecular thickness, mineral density and bone volume ratio of nonrunners were highly correlated with body mass (r2 = 0.824, p<0.05) and nonrunners were significantly heavier than runners (p<0.05). Adjusting for body mass revealed significantly thicker trabeculae in the posterior calcaneus of forefoot strikers, likely an artifact of greater running volume and earlier onset of running in this subgroup; thus, individuals with the greatest summative loading stimulus had, after body mass adjustment, the thickest trabeculae. Further study with larger sample sizes is necessary to elucidate the role of footstrike on calcaneal trabecular structure. To our knowledge, intraspecific body mass correlations with measures of trabecular robusticity have not been reported elsewhere. We hypothesize that early adoption of running and years of sustained moderate volume running stimulate bone modeling in trabeculae of the posterior calcaneus.

A Habitual Activity in Pre-industrial Rural and Urban Dutch Populations: A Study of Lower Limb Cross-sectional Geometry

This study combines historical data and the principles of bone functional adaptation to examine variation in terrestrial mobility in men and women from pre-industrial urban (Alkmaar 7M, 9F) and rural (Klaaskinderkerke 12M, 8F; Middenbeemster 21M, 22F) Dutch populations. Cross-sectional properties of the femoral and tibial midshaft are determined to investigate variation in lower limb mechanical loading. All populations had comparable age ranges. Rural Middenbeemster males had significantly more elliptically shaped tibiae compared to the other populations. Rural males from Klaaskinderkerke had significantly greater femoral cross-sectional area and torsional rigidity compared to females. In the tibia, the males from both rural populations had greater torsional rigidity and cross-sectional area compared to females. In the rural Middenbeemster population the males also had significantly more elliptically shaped tibiae compared to females. While no sexual dimorphism was found in the urban Alkmaar, significantly greater variation in lower limb cross-sectional properties was found for both males and females relative to the rural populations. These results conform to predictions based on the historical literature of greater lower limb loading in rural males compared to females as well as a greater variety of tasks performed in urban environments. The lack of significant differences in lower limb torsional rigidity or shape between populations in either sex suggests that rural life was not necessarily more physically strenuous than urban life in pre-industrial Dutch populations. However, variation in sexual dimorphism suggests that labor between males and females was differently organized in the rural and urban samples.

Mechanical loading effect to the functional bone adaptation

The loads on skeleton control bone turnover, rates of adapted remodeling and influence growth. Mechanical stimulus detected by osteocytes, is derived from muscle contraction or gravity forces. It is difficult to separate the effect of gravity from muscle contractions at bone mass. A great number of studies show that muscle contractions are present, significant and able to represent the large majority which causes the adaptive bone responses.

Microscale poroelastic metamodel for efficient mesoscale bone remodelling simulations

Bone functional tissue adaptation is a multiaspect physiological process driven by interrelated mechanical and biological stimuli which requires the combined activity of osteoclasts and osteoblasts. In previous work, the authors developed a phenomenological mesoscale structural modelling approach capable of predicting internal structure of the femur based on daily activity loading, which relied on the iterative update of the cross-sectional areas of truss and shell elements representative of trabecular and cortical bones, respectively. The objective of this study was to introduce trabecular reorientation in the phenomenological model at limited computational cost. To this aim, a metamodel derived from poroelastic microscale continuum simulations was used to predict the functional adaptation of a simplified proximal structural femur model. Clear smooth trabecular tracts are predicted to form in the regions corresponding to the main trabecular groups identified in literature, at minimal computational cost.

Mechanically induced bone formation is not sensitive to local osteocyte density in rat vertebral cancellous bone.

Osteocytes play an integral role in bone by sensing mechanical stimuli and releasing signaling factors that direct bone formation. The importance of osteocytes in mechanotransduction suggests that regions of bone tissue with greater osteocyte populations are more responsive to mechanical stimuli. To determine the effects of osteocyte population on bone functional adaptation we applied mechanical loads to the 8th caudal vertebra of skeletally mature female Sprague Dawley rats (6 months of age, n = 8 loaded, n = 8 sham controls). The distribution of tissue stress/strain within cancellous bone was determined using high-resolution finite element models, osteocyte distribution was determined using nano-computed tomography, and locations of bone formation were determined using three-dimensional images of fluorescent bone formation markers. Loading increased bone formation (3D MS/BS 10.82 ± 2.09% in loaded v. 3.17 ± 2.05% in sham control, mean ± SD). Bone formation occurred at regions of cancellous bone experiencing greater tissue stress/strain, however stress/strain was only a modest predictor of bone formation; even at locations of greatest stress/strain the probability of observing bone formation did not exceed 41%. The local osteocyte population was not correlated with locations of new bone formation. The findings support the idea that local tissue stress/strain influence the locations of bone formation in cancellous bone, but suggest that the size of the osteocyte population itself is not influential. We conclude that other aspects of osteocytes such as osteocyte connectivity, lacunocanilicular nano-geometry, and/or fluid pressure/shear distributions within the marrow space may be more influential in regulating bone mechanotransduction than the number of osteocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:672-681, 2018.

Horticultural activity predicts later localized limb status in a contemporary pre-industrial population.

Modern humans may have gracile skeletons due to low physical activity levels and mechanical loading. Tests using pre-historic skeletons are limited by the inability to assess behavior directly, while modern industrialized societies possess few socio-ecological features typical of human evolutionary history. Among Tsimane forager-horticulturalists, we test whether greater activity levels and, thus, increased loading earlier in life are associated with greater later-life bone status and diminished age-related bone loss. We used quantitative ultrasonography to assess radial and tibial status among adults aged 20+ years (mean ± SD age = 49 ± 15; 52% female). We conducted systematic behavioral observations to assess earlier-life activity patterns (mean time lag between behavioural observation and ultrasound = 12 years). For a subset of participants, physical activity was again measured later in life, via accelerometry, to determine whether earlier-life time use is associated with later-life activity levels. Anthropometric and demographic data were collected during medical exams. Structural decline with age is reduced for the tibia (female: -0.25 SDs/decade; male: 0.05 SDs/decade) versus radius (female: -0.56 SDs/decade; male: -0.20 SDs/decade), which is expected if greater loading mitigates bone loss. Time allocation to horticulture, but not hunting, positively predicts later-life radial status (βHorticulture = 0.48, p = 0.01), whereas tibial status is not significantly predicted by subsistence or sedentary leisure participation. Patterns of activity- and age-related change in bone status indicate localized osteogenic responses to loading, and are generally consistent with the logic of bone functional adaptation. Nonmechanical factors related to subsistence lifestyle moderate the association between activity patterns and bone structure.

Responses of MSCs to 3D Scaffold Matrix Mechanical Properties under Oscillatory Perfusion Culture.

Both fluid shear stress and matrix stiffness are implicated in bone metabolism and functional adaptation, but the synergistic action of these mechanical cues on the biological behaviors of mesenchymal stem cells (MSCs) is still not well-known. In the present work, a homemade oscillatory flow device was applied to investigate the effects of matrix stiffness on MSCs survival, distribution, and osteogenic differentiation in three-dimensional (3D) conditions. Furthermore, the flow field and cell growth in this bioreactor were theoretically simulated. The results demonstrated that oscillatory shear stress significantly increased the viability and distribution uniformity of MSCs throughout the scaffold after culture for 3 weeks. Compared to static culture, oscillatory shear stress could promote the collagen secretion, mineral deposits, and osteogenic differentiation of MSCs. The findings obtained from this work indicate that the oscillatory perfusion not only provides a higher survival rate and a more uniform distribution of cells but also facilitates osteogenic differentiation of MSCs. Oscillating perfusion bioreactor culture of MSCs in 3D scaffold with optimal matrix stiffness could offer an easy-to-use but efficient bioreactor for bone tissue engineering.

間質液流れを介した細胞間シグナル輸送が骨の機能的適応に及ぼす影響

間質液流れを介した細胞間シグナル輸送が骨の機能的適応に及ぼす影響

Bone Functionality and Division II Male and Female Collegiate Athletes from Multiple Sports

Participation in athletics is a risk factor for stress fracture however athletes are also viewed as icons of health, specifically bone health. Bone adaptation may vary depending on the type of loading; high or low impact sport. Are the tibiae of athletes involved in high impact sports (volleyball and soccer) functionally adapted compared to runners and swimmers? PURPOSE: To determine if Division II collegiate athletes had functionally adapted tibia (sufficient strength relative to body size) and whether functional adaptation can be determined from both the 25% and 50% tibial site. METHODS: No single variable indicates bone strength (Jepsen, 2013) and therefore cortical area (Ct.Ar), cortical bone mineral density (cBMD), moment of inertia (J) and bone strength (Strength-strain Index) were measured in 73 athletes (46 females and 27 males (age: 20.2 ± 1.7 yrs, body fat % 16.9 ± 7.5)) and 19 college student controls (8 females and 11 males (age: 23.3 ± 2.3 yrs, body fat % 21.1 ± 7.7)) using peripheral quantitative computed tomography (pQCT) at 25% and 50% of tibial length. Bone functionality was assessed by plotting bone strength vs loading (body weight x tibial length) and robustness (total area/length) vs loading. Based on the residuals from the regression, an athlete’s individual functionality was determined and two groups were formed (functionally adapted (FA) and under adapted (UA)). Student’s t-test detected differences. RESULTS: Height, weight, % body fat and tibial length were similar between the FA and UA groups. However, the FA female group had stronger (27%), more robust bones (23%), with larger moments of inertia (J) (33%) than the female UA group. Male FA group had similar cortical area and cBMD (P<0.05) as the male UA group but they had more robust (23%) stronger (26%) bones with larger J (32%). Both the 25% and 50% sites resulted in similar FA and UA groups and differences. Interestingly the FA and UA groups were comprised of athletes from all teams yet a majority of swimmers were found in the UA female group. CONCLUSIONS: Bone functional adaptation cannot be determined by anthropometric variables. FA groups had robust tibiae at the 25% and 50% site and larger J, allowing them to withstand the bending and torsional loads in sports. Determining bone functionality using the 25% or 50% site of the tibia yielded similar results.