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The skeleton is recognized as an last damaged organ in diabetes. The effects of diabetes on bone are complex and an area of active investigation. While most studies demonstrate that fracture risk is increased in both type 1 and type 2 diabetes, bone mineral density (BMD), as measured by dual-energy x-ray absorptiometry (DXA), may not reflect bone fragility or accurately predict fracture risk. This is particularly true in individuals with type 2 diabetes, in whom BMD is often normal or elevated compared with those without the disease. [ABSTRACT FROM AUTHOR]

Coxal bone, which is included in the structure of the pelvic skeleton, is in close relationship with the pelvic organs and great vessels. The aim of this study is to show the harmony between morphometric measurements using the correlation technique, based on the idea that the proportional harmony in different parts of our body will also be in the coxal bone. In the study, 95 dry coxal bone belonging to the Turkish population were examined. In dry bones of adults, the distance between anterior superior iliac spine and posterior superior iliac spine (A), distance between anterior inferior iliac spine and posterior inferior iliac spine (B), distance between anterior superior iliac spine and anterior inferior iliac spine (C), distance between posterior superior iliac spine and posterior inferior iliac spine (D), symphysial surface length (E), symphysial surface width (F), ischial tuberosity width (G), ischion-pubis arm thickness (H), coxal bone length (I), distance between the symphysial surface and the most protruding part of the ischial tuberosity (J) were measured with caliper. There was no statistical difference in the comparison of different measurements made on the right and left coxal bone in our study. In correlation studies, between (B) and (A) (r: 0.566), between (I) and (A) (r: 0.595), between (J) and (A) (r: 0.600), between (E) and (J) (r: 0.563) measurements showed a positive correlation relationship. In this study, excellent agreement was found in different morphometric measurements in coxal bone. [ABSTRACT FROM AUTHOR]

To facilitate rehabilitation training for patients, we proposed the implementation of an anthropomorphic exoskeleton structure that incorporates a variable instantaneous center of rotation (ICR). This design considers the variability in knee ICR among individuals, resulting from the irregular form of the human knee joint, and leverages a double-degrees-of-freedom (2DOF) five-bar mechanism to adapt to these differences. The walking gait of the human lower limb and the corresponding knee ICR were measured and calculated using an optical 3D motion capture system. The optimal dimension parameters of the five-bar mechanism were then obtained through the optimization of human movement position inputs and rod length constraints to minimize the error in knee ICR, gait angle, and ankle trajectory between the human and the exoskeleton. Finally, we established an exoskeleton prototype to conduct relevant experimental tests. The experiment results showed that the average errors of knee ICR trajectory, hip angle, knee angle, and ankle trajectory were 5.52 × 10−4 m, 0.010 rad, 0.014 rad, and 1.57 × 10−3 m, respectively. The experimental results demonstrated that the exoskeleton's movement trajectory was close to the human's, reducing the human–mechanism interaction force and improving patient comfort during rehabilitation training. [ABSTRACT FROM AUTHOR]

In this study, a new energetic hybrid skeleton was constructed through the integration of nitropyrazole and 1,3,4-oxadiazole skeletons in a molecule. Furthermore, the energetic precursor (2), the azo-bridged compound (3), the neutral nitramine (4) and the corresponding energetic salts (5e7) were synthesized. Their physicochemical and energetic properties were experimentally and theoretically evaluated. Among the developed compounds, the azo-bridged compound (3) and dihydroxylammoinium (6) display high detonation performances (3, Dv = 8904 m/s, P = 34.47 GPa; 6, Dv = 9025 m/s, P = 34.66 GPa), moderate sensitivities (3, IS = 16 J, FS = 120 N; 6, IS = 20 J, FS = 312 N) and good densities (3, 1.87 g/cm3; 6, 1.81 g/cm3), which indicates that they have the potential to replace the traditional high-energy explosive RDX. The results show that the integration of different energetic skeletons can achieve a good balance between energy and sensitivity. [ABSTRACT FROM AUTHOR]

In this paper we aim to address the topic of assisting the locomotion of a person with locomotor disabilities when climbing stairs. This assistance will be achieved with the help of a robotic system such as an exoskeleton. The designed exoskeleton must provide the step length corresponding to the distance between two steps, as well as the lifting height of the leg sufficient to step on the next stair step. For this purpose, an exoskeleton robotic system design solution is proposed. Based on this constructive solution, a virtual prototype of the robotic system will be realized, followed by a dynamic simulation, using software for dynamic analysis of multibody systems, namely ADAMS. The simulation results allow us to validate the design solution, on this conclusion we will proceed to the next stage of the research, namely the execution of an experimental prototype. [ABSTRACT FROM AUTHOR]

Infantile myofibromatosis (IM) is the most common benign fibrous tumor of infancy, characterized by the development of single or multiple nodules in the skin, soft tissues, bone, and/or viscera. Multicentric forms are less frequent and can affect different tissues simultaneously and their prognosis depends on their extension and visceral involvement. Rarely, these forms are limited to the skeleton, in which case the absence of extraosseous lesions makes it difficult to suspect this entity. We present the case of an infant with multiple radiolucent lesions involving the skull, ribs, spine, and long bones, discovered in a radiological study performed after a minor trauma. A broad differential diagnosis was considered based on the osteolytic and polyostotic nature of the lesions on imaging studies. This report details and illustrates the typical radiological findings in bony involvement of IM, which suggest this disorder over other diagnostic options. [ABSTRACT FROM AUTHOR]

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The article discusses the highlights of the 2021 Annual Conference of the International Society for Pediatric and Adolescent Diabetes (ISPAD) from the ISPAD Roving Reporters Team. Topics covered include a symposium on nutrition in diabetes, plenary session on diabetes pathogenesis, and symposium on skeletal growth in pediatric diabetes and obesity.

Ankylosing spondylitis is a chronic, debilitating arthritis with a predilection for the axial skeleton. It has a strong genetic predisposition, but the precise pathogenetic mechanisms involved in its development have not yet been fully elucidated. This has implications both for early diagnosis and for effective management. Recently, alterations in the intestinal microbiome have been implicated in disease pathogenesis. In this review, we summarize studies assessing the intestinal microbiome in AS pathogenesis, in addition to synthesizing the literature exploring the postulated mechanisms by which it exerts it pathogenic potential. Finally, we review studies analysing manipulation of the microbiome as a potential therapeutic avenue in AS management. [ABSTRACT FROM AUTHOR]

The regulation of whole-body homeostasis by the skeleton is mediated by its capacity to secrete endocrine signaling molecules. Although bone-derived hormones confer several adaptive benefits, their physiological functions also involve trade-offs, thus eventually contributing to disease. In this manuscript, we discuss the origins and functions of two of the best-studied skeletal mediators, fibroblast growth factor 23 and osteocalcin, in an evolutionary context. Moreover, we provide a theoretical framework seeking to explain the broad involvement of these two hormones in amniote physiology as well as their potential to fuel the development and progression of diseases. Vice versa, we outline which perturbations might be amenable to manipulation of these systems and discuss limitations and ongoing challenges in skeletal endocrine research. Finally, we summarize unresolved questions and potential future studies in this thriving field. [ABSTRACT FROM AUTHOR]

A hydrostatic skeleton allows a soft body to transmit muscular force via internal pressure. A human's tongue, an octopus' arm and a nematode's body illustrate the pervasive presence of hydrostatic skeletons among animals, which has inspired the design of soft engineered actuators. However, there is a need for a theoretical basis for understanding how hydrostatic skeletons apply mechanical work. We therefore modeled the shape change and mechanics of natural and engineered hydrostatic skeletons to determine their mechanical advantage (MA) and displacement advantage (DA). These models apply to a variety of biological structures, but we explicitly consider the tube feet of a sea star and the body segments of an earthworm, and contrast them with a hydraulic press and a McKibben actuator. A helical winding of stiff, elastic fibers around these soft actuators plays a critical role in their mechanics by maintaining a cylindrical shape, distributing forces throughout the structure and storing elastic energy. In contrast to a single-joint lever system, soft hydrostats exhibit variable gearing with changes in MA generated by deformation in the skeleton. We found that this gearing is affected by the transmission efficiency of mechanical work (MA×DA) or, equivalently, the ratio of output to input work. The transmission efficiency changes with the capacity to store elastic energy within helically wrapped fibers or associated musculature. This modeling offers a conceptual basis for understanding the relationship between the morphology of hydrostatic skeletons and their mechanical performance., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

79% of smartphone users carry their phone 22 hours a day. In this context, the main task worldwide, texting, is performed under a wide range of light and position conditions. The aim of this study was to test the effects of environmental illumination and screen brightness settings on upper limb and axial skeleton parameters. Twelve subjects performed three trials of texting under three experimental positions, two screen luminance settings and three environmental light conditions. 3 D axial skeleton and upper limb angles, smartphone orientation and face-to-smartphone distance were used as dependent variables. High environmental illumination and/or low screen brightness resulted in an increase in interaction time and a reduction in the face-to-smartphone distance by approximately 10%. Subjects attempted to compensate for the unfavourable effects of such light conditions by adopting postures rated 5 in the Rapid Upper Limb Assessment, indicating an increased risk of developing musculoskeletal disorders. Practitioner's summary: The purpose of the study was to quantify the joint angles of the upper body in experimental conditions that represent daily life. Postures were influenced by ambient illumination and display brightness. The most harmful postures were observed when the display brightness was minimum, and the ambient light was similar to a sunny day. Abbreviations: ST: seated with table; SWT: seated without any support; STA: standing; 0L: in the dark, no light; AL: ambient light; SL: strong light; BrightMin: minimum display brightness; BrightMax: maximum display brightness (BrightMax); ISB: International Society of Biomechanics; RULA: rapid upper limb assessment; MSDs: musculoskeletal disorders [ABSTRACT FROM AUTHOR]

We investigated the effects of calcium supplementation and physical practice on the bone ultrasound properties and trabecular microarchitecture in children. 160 children aged 8-11 were randomly allocated to active or nonactive groups and to receive either a calcium-phosphate or a placebo powder for 6 months. Skeletal status was assessed using an ultrasound technique, which measures the speed of sound (Ad-SoS, m/s) at the phalanx. Bone microarchitecture was characterized by fractal analysis measured on calcaneus radiographs and the result expressed as the Hmean parameter, that has been shown to a good reliability of the bone texture quality. After 6 months, the calcium group had significantly gained Ad-SoS compared to the placebo group (P = 0.01) and Hmean increase was greater in the active than the nonactive group (P < 0.05). Exercise and calcium supplementation had a differential effect on the bone tissue, calcium being rather linked to a systemic effect whereas exercise has acted better onto the skeletal stressed site. [ABSTRACT FROM AUTHOR]

The present study discussed about detailed examination of skeleton characters of four dugong specimens received from Indian Museum. The specimens were deposited and preserved in the National Zoological Collection (ZSI/27608; ZSI/27609; ZSI/27610; ZSI/27611) of The Mammal and Osteological Section, Zoological Survey of India, Kolkata. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional camera systems that integrate depth assessment with traditional two-dimensional images, such as the Microsoft Kinect, Intel Realsense, StereoLabs Zed and Orbecc, hold great promise as physical function assessment tools. When combined with point cloud and skeleton pose tracking software they can be used to assess many different aspects of physical function and anatomy. These assessments have received great interest over the past decade, and will likely receive further study as the integration of depth sensing and augmented reality smartphone cameras occurs more in everyday life.Research Question: The aim of this review is to discuss how these devices work, what options are available, the best methods for performing assessments and how they can be used in the future.Methods: Firstly, a review of the Microsoft Kinect devices and associated artificial intelligence, automated skeleton tracking algorithms is provided. This includes a narrative critique of the validity and clinical utility of these devices for assessing different aspects of physical function including spatiotemporal, kinematic and inverse dynamics data derived from gait and balance trials, and anatomical assessments performed using the depth sensor information. Methods for improving the accuracy of data are examined, including multiple-camera systems and sensor fusion with inertial monitoring units, model fitting, and marker tracking. Secondly, alternative hardware, including other structured light and time of flight methods, stereoscopic cameras and augmented reality leveraging smartphone and tablet cameras to perform measurements in three-dimensional space are summarised. Software options related to depth sensing cameras are then discussed, focussing on recent advances such as OpenPose and web-based methods such as PoseNet.Results and Significance: The clinical and non-laboratory utility of these devices holds great promise for physical function assessment, and recent developments could strengthen their ability to provide important and impactful health-related data. [ABSTRACT FROM AUTHOR]

This study captured neurophysiological, muscular, and perceptual adaptations to shoulder exoskeleton use during overhead work with competing physical-cognitive demands. Twenty-four males and females, randomly divided into control and exoskeleton groups, performed an overhead reaching and pointing task over three days without (single task) and with (dual task) a working memory task. Task performance, electromyography (EMG), neural activity, heart rate, and subjective responses were collected. While task completion time reduced for both groups at the same rate over days, EMG activity of shoulder muscles was lower for the exoskeleton group for both tasks, specifically for females during the dual task. Dual task reduced the physiological benefits of exoskeletons and neuromotor strategies to adapt to the dual task demands differed between the groups. Neuromuscular benefits of exoskeleton use were immediately realized irrespective of cognitive demand, however the perceptual, physiological, and neural adaptations with exoskeleton use were task- and sex-specific. • Sex differences in muscular effort during overhead tasks diminish with exoskeleton use. • Exoskeleton-related physiological adaptation during overhead tasks is longer in women. • Physiological benefits of exoskeleton use diminish with dual task demands. • Wearers don't perceive exoskeleton benefits with dual task demands. • Exoskeleton-related neural adaptation strategies differ with dual task demands. [ABSTRACT FROM AUTHOR]

Upper-limb exoskeletons are gaining traction in industrial work environments. However, other than advertised general specifications (e.g., peak support angle), the support torque provided throughout the reach envelope is largely unknown to end users. As such, this paper describes a methodology for measuring the specific supportive torque provided by upper-limb exoskeletons. The support of four commercially available passive upper-limb exoskeletons was quantified using an isokinetic dynamometer for all support ranges and levels (n = 68). Tests were repeated four times to determine between-session reliability. Intraclass correlation coefficients demonstrated 'Good' to 'Excellent' reliability, except for one condition. Polynomial regression equations were developed for each condition to predict exoskeleton support for any upper-limb elevation angle between 10° and 180°. These equations can be used to approximate upper-limb exoskeleton support in digital human modeling assessments, or to aid selection of exoskeleton settings specific to a worker's anthropometry and work task location. [Display omitted] • Isokinetic dynamometers can reliably measure upper-limb exoskeleton support. • Provided equations estimate exoskeleton support based on upper-limb elevation angle. • Exoskeleton support can be implemented into digital human modeling software. • These equations enable selection of exoskeleton settings for worker anthropometry. [ABSTRACT FROM AUTHOR]

The study of stress from an osteological perspective is challenging as we use skeletal remains to explore the lived experience and patterns of health. As an intricate overlap of multiple biological processes, the stress response system guides our understanding of how and why stress manifests as it does. Using traditional osteological methods of stress analysis, specifically cribra orbitalia, porotic hyperostosis, and enamel hypoplastic lesions, this study focuses on the relationship between these indicators to explore differences in stress manifestation in the Medieval and post‐Medieval periods in Denmark. Using the Black Friars cemetery population (13th–17th centuries), results show an increase in stress from the Medieval into the post‐Medieval period likely dictated by the strains of urbanism on a predominantly poor population. Additionally, a younger mean age at death was noted when multiple mild–moderate indicators were present as compared with one severe indicator being present. A recognition of the intricacies of the stress response effectively aids in the exploration of stress manifestation and the relationship, if any, between these well‐used skeletal indicators. [ABSTRACT FROM AUTHOR]

Climate changes driven by greenhouse gas emissions have been occurring in an accelerated degree, affecting environmental dynamics and living beings. Among all affected biomes, the Amazon is particularly subjected to adverse impacts, such as temperature rises and water acidification. This study aimed to evaluate the impacts of predicted climate change on initial growth and development of an important Amazonian food fish, the tambaqui. We analyzed growth performance, and monitored the initial osteogenic process and the emergence of skeletal anomalies, when larvae were exposed to three climate change scenarios: mild (B1, increase of 1.8°C, 200 ppm of CO2); moderate (A1B, 2.8°C, 400 ppm of CO2); and drastic (A2, 3.4°C, 850 ppm of CO2), in addition to a control room that simulated the current climatic conditions of a pristine tropical forest. The exposure to climate change scenarios (B1, A1B, and A2) resulted in low survival, especially for the animals exposed to A2, (24.7 ± 1.0%). Zootechnical performance under the B1 and A1B scenarios was higher when compared to current and A2, except for condition factor, which was higher in current (2.64 ± 0.09) and A1B (2.41 ± 0.14) scenarios. However, skeletal analysis revealed higher incidences of abnormalities in larvae exposed to A1B (34.82%) and A2 (39.91%) scenarios when compared to current (15.38%). Furthermore, the bone‐staining process revealed that after 16 days posthatch (7.8 ± 0.01 mm total length), skeletal structures were still cartilaginous, showing no mineralization in all scenarios. We concluded that tambaqui larvae are well‐adapted to high temperatures and may survive mild climate change. However, facing more severe climate conditions, its initial development may be compromised, resulting in high mortality rates and increased incidence of skeletal anomalies, giving evidence that global climate change will hamper tambaqui larvae growth and skeletal ontogeny. Climate change will affect Amazonian species due to increasing temperatures and water acidification. Newly‐hatched tambaqui larvae were exposed to three climate change scenarios for 16 days. Larvae growth and skeletal development were hindered and several skeletal anomalies appeared, especially in the drastic climate change scenario. [ABSTRACT FROM AUTHOR]

Abstract: Axolotl salamanders (Ambystoma mexicanum) remain aquatic in their natural state, during which biomechanical forces on their diarthrodial limb joints are likely reduced relative to salamanders living on land. However, even as sexually mature adults, these amphibians can be induced to metamorphose into a weight‐bearing terrestrial stage by environmental stress or the exogenous administration of thyroxine hormone. In some respects, this aquatic to terrestrial transition of axolotl salamanders through metamorphosis may model developmental and changing biomechanical skeletal forces in mammals during the prenatal to postnatal transition at birth and in the early postnatal period. To assess differences in the appendicular skeleton as a function of metamorphosis, anatomical and gene expression parameters were compared in skeletal tissues between aquatic and terrestrial axolotls that were the same age and genetically full siblings. The length of long bones and area of cuboidal bones in the appendicular skeleton, as well as the cellularity of cartilaginous and interzone tissues of femorotibial joints were generally higher in aquatic axolotls compared with their metamorphosed terrestrial siblings. A comparison of steady‐state mRNA transcripts encoding aggrecan core protein (ACAN), type II collagen (COL2A1), and growth and differentiation factor 5 (GDF5) in femorotibial cartilaginous and interzone tissues did not reveal any significant differences between aquatic and terrestrial axolotls. [ABSTRACT FROM AUTHOR]

Most studies utilizing fish to study the effects of simulated microgravity (SMG) only observe the effects during the first week of development. They also do not take into account the potential impact on development of vibrations caused by the equipment. In this study we analyze the effects of both SMG and vibration on development of the skeleton. We analyze three different exposure durations and starting points that coincide with cranial neural crest cell migration. We use a combination of bone staining and morphometrics to analyze the effects. Our data show that both vibration and SMG affect vertebra number and body size; however, not all vertebrae are equally affected by each treatment. We also show that delayed ossification manifests during development, particularly after SMG exposure, and this translates into buckled and bent bones in adults. This study highlights the large impact of even very short exposure periods when they coincide with critical time points of development. [ABSTRACT FROM AUTHOR]

The vitamin D history started early in the evolution of life (billion years ago) as a photochemical reaction producing an inert molecule. During the early evolution of vertebrates, this molecule became essential for calcium and bone homeostasis of terrestrial animals and arrived to the status of hormone. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. The major function of vitamin D is to maintain calcium homeostasis. It accomplishes this by increasing the efficiency of the intestine to absorb dietary calcium. When there is inadequate calcium in the diet to satisfy the body's calcium requirement, vitamin D communicates to the osteoblasts that signal osteoclast precursors to mature and dissolve the calcium stored in the bone. The typical "vitamin D-deficiency" disorder was observed for growing children in the west and south of England in the early 1600s. This disease was described by Glisson and named "rickets" (known also as "the English disease") and was observed with epidemic proportions in northern Europe and North America. The corrections of deformities of rickets were at the origin of the name "orthopedia" and of the technique of osteotomies. [ABSTRACT FROM AUTHOR]

Object skeleton is a useful geometric tool for shape analysis tasks. It encodes the topological structure of the primitive shape and preserves a geometric cue as well. Skeletonization is a seemingly simple but difficult research problem. A desirable skeletonization algorithm has to be topologically complete, insensitive to boundary noise, without any branch pruning and free of user-specified parameters. In this paper, we propose a novel method based on the heat equation to extract skeletons assuming that the input is a binary image. Based on the connection between the skeleton and ridge lines, we use the smooth heat diffusion height surface to approximate the real distance field, and then extract the ridge lines of the surface as the output skeleton. Different from the existing approaches, the proposed method in this paper has the above-mentioned excellent properties and can capture the clean and stable skeleton directly. Extensive experimental results show that the new approach can yield better skeletons than the state-of-the-art. [ABSTRACT FROM AUTHOR]

Bisphosphonates are considered the most effective drugs for controlling adult and pediatric osteolytic diseases. Although they have been used successfully for many years, several side effects, such as osteonecrosis of the jaw, delayed dental eruption, atypical femoral fracture, and alterations to the bone growth system, have been described. After an overview of nitrogenous bisphosphonate, the purpose of this article is to describe their mechanisms of action and current applications, review the preclinical and clinical evidence of their side effects in the skeleton (“what we know”), and describe current recommendations for preventing and managing these effects (“what we can do”). Finally, promising future directions on how to limit the occurrence of these side effects will be presented. [ABSTRACT FROM AUTHOR]

Body mass is estimated from skeletal records with low accuracy, and it is expected that population-specific equations derived by a hybrid approach may help to reduce the error in body mass estimates. We used 204 individuals from five Central European Early Medieval sites to test the effect of population-specific femoral head breadth equations on the accuracy of body mass estimates. The baseline for living body mass was computed using the biiliac breadth and stature. We also analyzed the agreement of five general femoral head techniques that are used in body mass estimation (Elliott et al. (Archaeol Anthropol Sci 1-20, 2015b; Grine et al. (Am J Phys Anthropol 97:151-185, 1995); McHenry (Am J Phys Anthropol 87:407-431, 1992); Ruff et al. (Am J Phys Anthropol 148:601-617, 2012); Ruff et al. (Am J Phys Anthropol 86:397, 1991)). Our results support previous findings showing that body mass is predicted with lower accuracy than stature, even when population-specific equations are derived. However, the population-specific approach increases the agreement with the body mass estimated from the biiliac breadth and stature, particularly when sex-specific equations are used. Thus, our results advocate for the employment of sex-specific equations when possible and show that the possibility of deriving equation for each sex separately is the main advantage of the population-specific approach. The best agreement among the body mass techniques in the Central European Early Medieval samples was observed using the femoral head equations reported by Ruff et al. (Am J Phys Anthropol 148:601-617, 2012) and McHenry (Am J Phys Anthropol 87:407-431, 1992), whereas other studied equations provided lower agreement. The particularly low performance obtained using the technique reported by Elliott et al. (2015b) questioned the use of their equations to estimate body masses. [ABSTRACT FROM AUTHOR]

The skeleton has recently emerged as a critical insulin target tissue that regulates whole body glucose metabolism and male reproductive function. While our understanding of these new regulatory axes remains in its infancy, the bone‐specific protein, osteocalcin, has been shown to be centrally involved. Undercarboxylated osteocalcin acts as a secretagogue in a feed‐forward loop to stimulate pancreatic β‐cell proliferation and insulin secretion, improve insulin sensitivity, and promote testosterone production. Importantly, dysregulation of insulin signaling in bone causes a reduction in serum osteocalcin levels that is associated with elevated blood glucose and reduced serum insulin levels, suggesting that the skeleton may play a significant role in the development of diet‐induced insulin resistance. Insulin signaling is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1) which becomes hyper‐activated in response to nutrient overload. Loss‐ and gain‐of function models suggest that mTORC1 function in bone is essential for normal skeletal development; however, the role of this complex in the regulation of glucose metabolism remains to be determined. This review highlights our current understanding of the role played by osteocalcin in the skeletal regulation of glucose metabolism and fertility. In particular, it examines data emerging from transgenic mouse models which have revealed a pancreas‐bone‐testis regulatory axis and discusses recent human studies which seek to corroborate findings from mouse models with clinical observations. Moreover, we review recent studies which suggest dysregulation of insulin signaling in bone leads to the development of insulin resistance and discuss the potential role of mTORC1 signaling in this process. [ABSTRACT FROM AUTHOR]

Introduction: The development of skeletal structures (cranial base, upper and lower) and upper airways spaces (oropharyngeal and nasopharyngeal) of the skull has always been an issue of great interest in orthodontics. Foetal MRI images obtained as screening exam during pregnancy can help to understand the development of these structures using a sample cephalometric analysis.Material and Methods: A total of 28 MRI images in sagittal section of foetuses from 20th to 32th weeks of gestation were obtained to dispel doubts about the presence of skeletal malformations. Cephalometric measurements were performed on MRI T2-dependent images acquired with a 1.5 T scanner. The Software Osirix 5 permits to study sagittal and vertical dimensions of the skull analysing linear measurements, angles and areas of the skeletal structures.Results: Vertical and sagittal dimension of cranial base, maxilla and mandible grow significantly (P < .01) between the second and third trimester of gestational period as well as nasopharyngeal and oropharyngeal spaces (P < .05). High correlation between the development of anterior cranial base and functional areas devoted to speech and swallow is demonstrated (r: .97).Conclusions: The development of craniofacial structures during foetal period seems to show a close correlation between skeletal features and functional spaces with a peak between the second and third trimester of gestation. MRI images result helpful for the clinician to detect with a sample cephalometric analysis anomalies of skeletal and functional structures during prenatal period. [ABSTRACT FROM AUTHOR]

Purpose Physeal fractures in children frequently give rise to concerns about the condition of the growth plate. Our observations have proven that the dysfunction of the growth plate is less frequent complication in those cases than misdiagnosed interposition of the periosteum. The aim of this paper is to familiarize the readers with the issue of treatment of physeal fractures of the distal tibia and fibula in the growing skeleton. Materials and methods We analyzed the group of 75 patients – children and adolescents – with surgically treated physeal fractures of the lower leg. The analysis included age, sex, circumstances of trauma infliction, type of sustained damage, employed therapeutic technique, timing of surgical procedure, duration of hospitalization, complications, duration of follow-up, radiological and functional results according to the AOFAS scale. Results The group consisted of 23 girls and 52 boys. The mean age was 13.6 years. The most frequent cause of trauma was same-level fall, usually during sports activities (35 cases). The most common type of damage was Salter-Harris type II fracture (35 cases). Among the employed surgical techniques, open reduction and stabilization with K-wires was the most often used (52 cases). A group of four patients attracted our attention, in whom after a closed reduction, signs of periosteum interposition were noted. These patients required a second procedure. In one patient, the growth plate arrest occurred; it was directly caused by local osteomyelitis. Conclusions With adequately conducted treatment of distal tibia and distal fibula physeal fractures, the results are good. Misdiagnosed periosteum interposition poses a more serious clinical problem as opposed to the commonly anxiety-provoking post-traumatic growth plate dysfunction. [ABSTRACT FROM AUTHOR]

The bone marrow niche is a dynamic and complex microenvironment that can both regulate, and be regulated by the bone matrix. Within the bone marrow (BM), mesenchymal stromal cell (MSC) precursors reside in a multi-potent state and retain the capacity to differentiate down osteoblastic, adipogenic, or chondrogenic lineages in response to numerous biochemical cues. These signals can be altered in various pathological states including, but not limited to, osteoporotic-induced fracture, systemic adiposity, and the presence of bone-homing cancers. Herein we provide evidence that signals from the bone matrix (osteocytes) determine marrow adiposity by regulating adipogenesis in the bone marrow. Specifically, we found that physiologically relevant levels of Sclerostin (SOST), which is a Wnt-inhibitory molecule secreted from bone matrix-embedded osteocytes, can induce adipogenesis in 3T3-L1 cells, mouse ear- and BM-derived MSCs, and human BM-derived MSCs. We demonstrate that the mechanism of SOST induction of adipogenesis is through inhibition of Wnt signaling in pre-adipocytes. We also demonstrate that a decrease of sclerostin in vivo, via both genetic and pharmaceutical methods, significantly decreases bone marrow adipose tissue (BMAT) formation. Overall, this work demonstrates a direct role for SOST in regulating fate determination of BM-adipocyte progenitors. This provides a novel mechanism for which BMAT is governed by the local bone microenvironment, which may prove relevant in the pathogenesis of certain diseases involving marrow adipose. Importantly, with anti-sclerostin therapy at the forefront of osteoporosis treatment and a greater recognition of the role of BMAT in disease, these data are likely to have important clinical implications. [ABSTRACT FROM AUTHOR]

Background and objective: Physiological cross-sectional area (PCSA) of a muscle plays a significant role in determining the force contribution of muscle fascicles to skeletal movement. This parameter is typically calculated from the lengths of muscle fibres selectively sampled from the superficial layer of the muscle. However, recent studies have found that the length of fibres in the superficial layer often differs significantly ( p  < 0.5) from the length of fibres in the deep layer. As a result, PCSA estimation is inaccurate. In this paper, we propose a method to automatically reconstruct fibres in the whole volume of a muscle from those selectively sampled on the superficial layer. Methods: The method performs a centripetal Catmull–Rom interpolation of the input fibres within the volume of a muscle represented by its 3D surface model, automatically distributing the fibres among multiple heads of the muscle and shortening the deep fibres to support large attachment areas with extremely acute angles. Results: Our C++ implementation runs in a couple of seconds on commodity hardware providing realistic results for both artificial and real data sets we tested. Conclusions: The fibres produced by the method can be used directly to determine the personalised mechanical muscle functioning. Our implementation is publicly available for the researchers at https://mi.kiv.zcu.cz/ . [ABSTRACT FROM AUTHOR]

Organisms are organized into suites of anatomical structures that typically covary when developmentally or functionally related, and this morphological integration plays a determinant role in evolutionary processes. Artificial selection on domestic species causes strong morphological changes over short time spans, frequently resulting in a wide and exaggerated phenotypic diversity. This raises the question of whether integration constrains the morphological diversification of domestic species and how natural and artificial selection may impact integration patterns. Here, we study the morphological integration in the appendicular skeleton of domestic horses and donkeys, using three-dimensional geometric morphometrics on 75 skeletons. Our results indicate that a strong integration is inherited from developmental mechanisms which interact with functional factors. This strong integration reveals a specialization in the locomotion of domestic equids, partly for running abilities. We show that the integration is stronger in horses than in donkeys, probably because of a greater degree of specialization and predictability of their locomotion. Thus, the constraints imposed by integration are weak enough to allow important morphological changes and the phenotypic diversification of domestic species. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a medically supervised, high fat, low carbohydrate and restricted protein diet which has been used successfully in patients with refractory epilepsy. Only one published report has explored its effect on the skeleton. We postulated that the KD impairs skeletal health parameters in patients on the KD. Patients commenced on the KD were enrolled in a prospective, longitudinal study, with monitoring of Dual-energy X-ray absorptiometry (DXA) derived bone parameters including bone mineral content and density (BMD). Areal BMD was converted to bone mineral apparent density (BMAD) where possible. Biochemical parameters, including Vitamin D, and bone turnover markers, including osteocalcin, were assessed. Patients were stratified for level of mobility using the gross motor functional classification system (GMFCS). 29 patients were on the KD for a minimum of 6 months (range 0.5-6.5 years, mean 2.1 years). There was a trend towards a reduction in lumbar spine (LS) BMD Z score of 0.1562 (p = 0.071) per year and 20 patients (68%) had a lower BMD Z score at the end of treatment. While less mobile patients had lower baseline Z scores, the rate of bone loss on the diet was greater in the more mobile patients (0.28 SD loss per year, p = 0.026). Height adjustment of DXA data was possible for 13 patients, with a mean reduction in BMAD Z score of 0.19 SD. Only two patients sustained fractures. Mean urinary calcium-creatinine ratios were elevated (0.77), but only 1 patient developed renal calculi. Children on the KD exhibited differences in skeletal development that may be related to the diet. The changes were independent of height but appear to be exaggerated in patients who are ambulant. Clinicians should be aware of potential skeletal side effects and monitor bone health during KD treatment. Longer term follow up is required to determine adult/peak bone mass and fracture risk throughout life. [ABSTRACT FROM AUTHOR]

The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease. [ABSTRACT FROM AUTHOR]

Throughout the last decade, significant developments in cellular, molecular and mouse models have revealed major endocrine functions of the skeleton. More recent studies have evolved the interplay between bone-specific hormones, the skeleton, marrow adipose tissue, muscle and the brain. This review focuses on literature from the last decade, addressing the endocrine regulation of global energy metabolism via the skeleton. In addition, we will highlight several recent studies that further our knowledge of new endocrine functions of some organs; explore remaining unanswered questions; and, finally, we will discuss future directions for this more complex era of bone biology research. [ABSTRACT FROM AUTHOR]

Steroids are important components of cell membranes and are involved in several physiological functions. A diphenylmethane (DPM) skeleton has recently been suggested to act as a mimetic of the steroid skeleton. However, difficulties are associated with efficiently introducing different substituents between two phenyl rings of the DPM skeleton, and, thus, further structural development based on the DPM skeleton has been limited. We herein developed an efficient synthetic method for introducing different substituents into two phenyl rings of the DPM skeleton. We also synthesized DPM-based estrogen receptor (ER) modulators using our synthetic method and evaluated their ER transcriptional activities. [ABSTRACT FROM AUTHOR]

A carcass of a House Swift ( Apus nipalensis) found in Ladner, British Columbia on 18 May 2012 appears to be the first documented record of this species in the Americas. Identification is based on DNA sequencing and morphometric characters. University of British Columbia Beaty Biodiversity Museum Cowan Tetrapod Collection catalogue number B017056 has been assigned to this specimen (round study skin, spread wing, partial skeleton, and tissue samples). [ABSTRACT FROM AUTHOR]

Background: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult life. Objective: The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults. Design: Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining 1) the effects of "high versus low" protein intake or 2) dietary protein's synergistic effect with Ca±D intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments. Strength of evidence was rated by group consensus. Random-effects meta-analyses for outcomes with ≥4 RCTs were performed. Results: Sixteen RCTs and 20 prospective cohort studies were included in the systematic review. Overall ROB was medium. Moderate evidence suggested that higher protein intake may have a protective effect on lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake (net percentage change: 0.52%; 95% CI: 0.06%, 0.97%, I²: 0%; n = 5) but no effect on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers. Limited evidence did not support an effect of protein with Ca±D on LS BMD, TH BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall fractures. Conclusions: Current evidence shows no adverse effects of higher protein intakes. Although there were positive trends on BMD at most bone sites, only the LS showed moderate evidence to support benefits of higher protein intake. Studies were heterogeneous, and confounding could not be excluded. High-quality, long-term studies are needed to clarify dietary protein's role in bone health. This trial was registered at www.crd.york.ac.uk as CRD42015017751. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a marker of degeneration within the skeleton, frequently associated with age. This study quantifies the correlation between OA and age-at-death and investigates the utility of shoulder OA as a forensic age indicator using a modern North American sample of 206 individuals. Lipping, surface porosity, osteophyte formation, eburnation, and percentage of joint surface affected were recorded on an ordinal scale and summed to create composite scores that were assigned a specific phase. Spearman's correlation indicated a positive relationship between each composite score and age (right shoulder = 0.752; left shoulder = 0.734). Transition analysis revealed a tendency toward earlier degeneration of the right shoulder. Bayesian statistics generated phase-related age estimates based on highest posterior density regions. Best age estimates were into the seventh decade at the 90th and 50th percentile. The proposed method supplements traditional techniques by providing age estimates beyond a homogenous 50+ age cohort. [ABSTRACT FROM AUTHOR]

The study of human growth and skeletal development by human biologists is framed by the larger theoretical concerns regarding the underpinnings of population variation and human evolution. This unique perspective is directly relevant to the assessment of child health and well-being at the individual and group level, as well as the construction of growth charts. Environmental, behavioral (nutrition and physical activity), and disease-related factors can prevent attainment of full genetic potential for growth. Undernutrition is most often the cause of growth faltering and poor skeletal development. Disease related factors, such as malabsorption, inflammation, and immobility also have profound effects. These effects will be illustrated with examples from diseases such as cystic fibrosis, inflammatory bowel disease, and Down syndrome. The need for separate growth charts for children with genetic disorders is often controversial because of potential medical and/or nutritional complications associated with some disorders. Children with Alagille syndrome and Down syndrome will be used to illustrate the advantages and limitations of syndrome-specific charts. This overview of health and disease effects on growth and skeletal development provides insights into the plasticity of human growth and its sensitivity to overall health and well-being. [ABSTRACT FROM AUTHOR]

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. [ABSTRACT FROM AUTHOR]

Bone marrow stromal cells maintain the adult skeleton by forming osteoblasts throughout life that regenerate bone and repair fractures. We discovered that subsets of these stromal cells, osteoblasts, osteocytes, and hypertrophic chondrocytes secrete a C-type lectin domain protein, Clec11a, which promotes osteogenesis. Clec11a-deficient mice appeared developmentally normal and had normal hematopoiesis but reduced limb and vertebral bone. Clec11a-deficient mice exhibited accelerated bone loss during aging, reduced bone strength, and delayed fracture healing. Bone marrow stromal cells from Clec11a-deficient mice showed impaired osteogenic differentiation, but normal adipogenic and chondrogenic differentiation. Recombinant Clec11a promoted osteogenesis by stromal cells in culture and increased bone mass in osteoporotic mice in vivo. Recombinant human Clec11a promoted osteogenesis by human bone marrow stromal cells in culture and in vivo. Clec11a thus maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. In light of this, we propose to call this factor Osteolectin. [ABSTRACT FROM AUTHOR]

Bone renews itself and changes shape throughout life to account for the changing needs of the body; this requires co-ordinated activities of bone resorbing cells (osteoclasts), bone forming cells (osteoblasts) and bone’s internal cellular network (osteocytes). This review focuses on paracrine signaling by the IL-6 family of cytokines between bone cells, bone marrow, and skeletal muscle in normal physiology and in pathological states where their levels may be locally or systemically elevated. These functions include the support of osteoclast formation by osteoblast lineage cells in response to interleukin 6 (IL-6), interleukin 11 (IL-11), oncostatin M (OSM) and cardiotrophin 1 (CT-1). In addition it will discuss how bone-resorbing osteoclasts promote osteoblast activity by secreting CT-1, which acts as a “coupling factor” on osteocytes, osteoblasts, and their precursors to promote bone formation. OSM, produced by osteoblast lineage cells and macrophages, stimulates bone formation via osteocytes. IL-6 family cytokines also mediate actions of other bone formation stimuli like parathyroid hormone (PTH) and mechanical loading. CT-1, OSM and LIF suppress marrow adipogenesis by shifting commitment of pluripotent precursors towards osteoblast differentiation. Ciliary neurotrophic factor (CNTF) is released as a myokine from skeletal muscle and suppresses osteoblast differentiation and bone formation on the periosteum (outer bone surface in apposition to muscle). Finally, IL-6 acts directly on marrow-derived osteoclasts to stimulate release of “osteotransmitters” that act through the cortical osteocyte network to stimulate bone formation on the periosteum. Each will be discussed as illustrations of how the extended family of IL-6 cytokines acts within the skeleton in physiology and may be altered in pathological conditions or by targeted therapies. [ABSTRACT FROM AUTHOR]

Mesenchymal chondrosarcomas (MC) are rare and aggressive forms of chondrosarcoma. They are distinct tumors arising in unicentric or multicentric locations from both skeletal and extraskeletal tissues. The most affected region is the facial skeleton, especially the jaws. In this report, we present a case of MC primarily involving the mandible in a 60-year-old female patient. [ABSTRACT FROM AUTHOR]

In total 110 skeletons recovered from the Late Bronze Age (ca. 1100/900–760/500 cal. BC) cemetery Liushui, Autonomous Region Xinjiang, China (36°14′41.9″N, 81°43′23″E, ca. 2850 m a.s.l.) were suitable for observation of entheseal changes (EC presence which does not involve inferring soft tissue changes) and stress fractures. Four fibrocartilaginous entheses (lateral and medial epicondyles, the attachment sites of the quadriceps muscle at the patella and the patellar ligament, and the Achilles' tendon at the calcaneus) and one fibrous enthesis (plantar aponeurosis at the calcaneus) were scored in skeletons with respective anatomical structures preserved. Some variations in EC percentage values in relation to sex and age are documented, though the relatively small sample size limits robustness of statistical interpretation. Our results do not fully support age-related EC increase. Only medial epicondylosis and lower calcaneal spur show the most frequent occurrence in the 56–70 years age group, with substantially higher scores compared to the other age groups. Both tendinitis patellae and dorsal calcaneal spur have their highest scores in the 15–23 years age group. Dorsal spur, tendinitis patellae and lateral epicondylosis are substantially higher among the female individuals than in the male skeletal remains from Liushui. Being compared with European prehistoric and industrial populations and with Californian historic hunter–gatherers, the EC prevalence of the Liushui population indicates high physical activity levels with serious injury hazard. Grave goods and absolute chronology identify the Liushui population as mobile pastoralists at an early stage of the emergence of complex mounted pastoralism as a new economic and social system in Central Asia. The chronic nature of EC in the Liushui population, particularly noticeable in the female skeletons, may suggest an insufficient time for adaptation to permanent mechanical stress unavoidable in the prevalent mountainous environments. Relatively small sample size and the multifactorial etiology of EC require cautious evaluation of the obtained results. However, given the scarcity of palaeopathological records from the study region, our reconstructions and interpretations from the high-mountain Liushui site can be offered as a frame for further testing. [ABSTRACT FROM AUTHOR]

Little is known about the population variability of the demographic structure in premodern Japan, because of the lack of demographic data from regions peripheral to Japan. This study examines the human skeletal remains of early modern agriculturalists in Kumejima (Okinawa) and estimates age-at-death distributions using systems of auricular surface aging following Lovejoy et al. and Buckberry and Chamberlain to reveal demographic trends in premodern Japan. The materials studied consisted of 221 human skeletal remains of the early modern period from the Yacchi-no-gama stalactite cave and Kanjinbaru sites in Kumejima. Application of the Bayesian theorem to Buckberry and Chamberlain's age-at-death estimation was based on known-age modern collections from Japan and Spitalfields (UK), assuming uniform, reference, and model prior probabilities. Despite the differences in aging methodologies, some consistent results were obtained: 1) the Japanese skeletal series showed variability in age-at-death structure in the past and 2) the Kumejima contained higher proportions of elderly individuals compared to the Jomon, Okhotsk, and Kamakura populations, but had similar or slightly higher proportions of elderly compared to/than populations from Edo. The results of this study imply that the Kumejima might have been one of the most long-lived populations in premodern Japan. They also revealed demographic trends that could not otherwise be reconstructed from historical or ethnological records. [ABSTRACT FROM AUTHOR]

This study compared variation in size, function and sport-specific technical skills of youth soccer players associated with differences in biological maturity status. 60 male soccer players of under-14 (U14) and under-17 (U17) categories were submitted to anthropometric and body composition measurements as well as motor and soccer-specific technical skill tests. Skeletal maturity was determined by skeletal age. Athletes of both categories were classified as early, on-time or late-maturing, according to the difference between chronological age and skeletal age. Body mass and height were lower in the late athletes, independent of category (P<0.01). Differences in adiposity were found only between athletes of the U14 (late< early, P<0.05). Statistically significant differences were identified on aerobic endurance in U14 (early

The evolution of the investment in exaggerated secondary sexual traits is a topic of great interest for scientists. Despite antlers in the family Cervidae being one of the most interesting allometric structures, the nature of the relationships between antler and body size, and the influence of physiological factors driving the evolution of these characters, still remain unclear. In this paper, I examine these relationships in depth using the largest sample size ever studied (43 species). Under the hypothesis that antler growth may be limited by skeleton size as this process requires the allocation of huge amounts of mineral resources to the antlers, skeleton-related variables may more accurately explain these allometric relationships. The existence of physiological constraints should therefore be more clearly highlighted when studying the relationships between body size variables and the relative investment in the antler (measured as length or mass of antler per kg of skeleton). Results show that antler length is best described as being linearly related to head-body length rather than other measurements of size, and antler weight has a quadratic relationship with body mass. However, the relative investment in antler length (related to skeleton mass) is independent of body size variables, while the relative investment in antler mass has a quadratic relationship with shoulder height. The results obtained for antler mass reflect the existence of physiological constraints in the evolution of antlers, which are greater for larger sized species. On the other hand, the evolution of antler length may be linked to other factors, most probably sociobiological and biomechanical ones. [ABSTRACT FROM AUTHOR]

In the winter Olympic sport of Skeleton, sliders sprint and load themselves onto the sled facing head forwards. The slider uses primarily their shoulders and torso to apply control to the direction of the sled as it progressively gains speed during its descent. These small control course keeping maneuvers alongside more severe use of toe tapping onto the ice will help determine the eventual trajectory of the sled. It is therefore of interest to consider for a possible trajectory what control actions will determine the fastest descent time and in particular what metrics should be examined. In this paper a three degree-of-freedom simulation has been developed to analyse the influence of different control strategies on the descent time of a bob-skeleton. A proportional-derivative (PD) controller is used to steer the simulation down a representation of the Igls ice-track. Parametric variations of the simulation's performance were analysed and compared to identify possible correlations for controllers assist the design of an optimal controller. Analysis of the results have identified positive correlations between descent time, transverse distance travelled and energy dissipation establishing that the fastest descent time is achieved by minimising the energy lost through the descent. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs 1 ). Methods Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1 + hSSC 1 function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb 2 ), ii) machined Ti surface group in osteogenic media (Mo 3 ), iii) LASER-modified Ti group in basal media (Lb 4 ) and, iv) LASER-modified Ti group in osteogenic media (Lo 5 ). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP 6 ) specific activity), live/dead immunostaining (Cell Tracker Green (CTG 7 )/Ethidium Homodimer-1 (EH-1 8 )), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs 1 on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP 6 specific activity on the hSSCs 1 -seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP 6 and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions LASER-modified Ti surfaces modify the behaviour of hSSCs. 1 In particular, SSC 1 adhesion, osteogenic gene expression, cell morphology and cytoskeleton structure were affected. The current studies show Ti LASER modification can enhance the osseointegration between Ti and skeletal cells, with important implications for orthopaedic application. [ABSTRACT FROM AUTHOR]

Physical and biochemical cues play fundamental roles in the skeleton at both the tissue and cellular levels. The precise coordination of these cues is essential for skeletal development and homeostasis, and disruption of this coordination can drive disease progression. The growth factor TGFβ is involved in both the regulation of and cellular response to the physical microenvironment. It is essential to summarize the current findings regarding the mechanisms by which skeletal cells integrate physical and biochemical cues so that we can identify and address remaining gaps that could ultimately improve skeletal health. In this review, we describe the role of TGFβ in mechanobiological signaling in bone and cartilage at the tissue and cellular levels. We provide detail on how static and dynamic physical cues at the macro-level are transmitted to the micro-level, ultimately leading to regulation at each level of the TGFβ pathway and to cell differentiation. The continued integration of engineering and biological approaches is needed to answer many remaining questions, such as the mechanisms by which cells generate a coordinated response to physical and biochemical cues. We propose one such mechanism, through which the combination of TGFβ and an optimal physical microenvironment leads to synergistic induction of downstream TGFβ signaling. [ABSTRACT FROM AUTHOR]