Skeletal Adaptations Research Articles

The comparative and functional anatomy of the forelimb muscle architecture of Humboldt's woolly monkey (Lagothrix lagotricha).

Humboldt's woolly monkey (Lagothrix lagortricha) is a ceboid primate that more frequently engages in plantigrade quadrupedalism (~89%) but is, like most other members of the subfamily Atelinae, capable of suspensory postures and "tail assisted" brachiation. That taxon's decreased reliance on suspension is reflected in the skeletal anatomy of the upper limb which is less derived relative to more frequently suspensory atelines (Ateles, Brachyteles) but is in many ways (i.e., phalangeal curvature, enlarged joint surfaces, elongated diaphyses) intermediate between highly suspensory and quadrupedal anthropoids. Although it has been suggested that muscle may have morphogenetic primacy with respect to bone this has not been explicitly tested. The present study employs analyses of Lagothrix upper limb muscle fiber length, relative physiological cross-sectional area and relative muscle mass to test whether muscular adaptations for suspensory postures and locomotion in Lagothrix precede adaptive refinements in the skeletal tissues or appear more gradually in conjunction with related skeletal adaptations. Results demonstrate that Lagothrix upper limb musculature is most like committed quadrupeds but that limited aspects of the relative distribution of segmental muscle mass may approach suspensory hylobatids consistent with only a limited adaptive response in musculature prior to bone. Results specific to the shoulder were inconclusive owing to under-representation of quadrupedal shoulder musculature and future work should be focused more specifically on the adaptive and functional morphology of the muscular anatomy and microstructure of the scapulothoracic joint complex.

Modeling implications of the relationship between active and passive skeletal muscle mechanical properties

It is challenging to obtain in vivo or in situ experimental data from human muscles due to the invasive nature of such measurements. As a result, many investigations of human performance, surgery, or skeletal adaptation are necessarily based on musculoskeletal models. The utility of such models will depend on the question being asked and the extent to which the model is sufficiently accurate to address that question. In this perspective article, we take advantage of unique intraoperative access to the human gracilis muscle and make direct comparisons between commonly modeled parameters and those measured from the human gracilis. We directly compare muscle–tendon unit (MTU) length, optimal fiber length, and tendon slack length. Our results demonstrate that measured and modeled length parameters differ greatly. This is primarily due to the fact that slack muscle length and optimal muscle length differ greatly for the human gracilis and that models assume they are the same length.

Evolutionary integration of forelimb and hindlimb proportions within the bat wing membrane inhibits ecological adaptation.

Bats and birds are defined by their convergent evolution of flight, hypothesized to require the modular decoupling of wing and leg evolution. Although a wealth of evidence supports this interpretation in birds, there has been no systematic attempt to identify modular organization in the bat limb skeleton. Here we present a phylogenetically representative and ecologically diverse collection of limb skeletal measurements from 111 extant bat species. We compare this dataset with a compendium of 149 bird species, known to exhibit modular evolution and anatomically regionalized skeletal adaptation. We demonstrate that, in contrast to birds, morphological diversification across crown bats is associated with strong trait integration both within and between the forelimb and hindlimb. Different regions of the bat limb skeleton adapt to accommodate variation in distinct ecological activities, with flight-style variety accommodated by adaptation of the distal wing, while the thumb and hindlimb play an important role facilitating adaptive responses to variation in roosting habits. We suggest that the wing membrane enforces evolutionary integration across the bat skeleton, highlighting that the evolution of the bat thumb is less correlated with the evolution of other limb bone proportions. We propose that strong limb integration inhibits bat adaptive responses, explaining their lower rates of phenotypic evolution and relatively homogeneous evolutionary dynamics in contrast to birds. Powered flight, enabled by the membranous wing, is therefore not only a key bat innovation but their defining inhibition.

Vertebral morphology and intracolumnar variation of the iconic African viperid snake Atheris (Serpentes, Viperidae).

We here provide a detailed description of the vertebral morphology of the African arboreal viperid snakes of the genus Atheris. Vertebrae of three different species of the genus, i.e., Atheris desaixi, Atheris hispida, and Atheris katangensis, were investigated via the aid of μCT (micro-computed tomography) scanning. We describe several vertebrae from different regions of the vertebral column for all three species, starting from the atlas-axis complex to the caudal tip, in order to demonstrate important differences regarding the intracolumnar variation. Comparison of these three species shows an overall similar general morphology of the trunk vertebrae among the Atheris species. We extensively compare Atheris with other known viperids. As the sole arboreal genus of Viperinae the prehensile nature of the tail of Atheris is reflected in its caudal vertebral morphology, which is characterized by a high number of caudal vertebrae but also robust and anteroventrally oriented pleurapophyses as a skeletal adaptation, linked with the myology of the tail, to an arboreal lifestyle. We anticipate that the extensive figuring of these viperid specimens will also aid identifications in paleontology.

Minimal Impact of Age on Adaptive Bone Formation in the Distal Tibia of US Army Basic Combat Trainees: The ARMI Study

ABSTRACT Introduction Although bone formation has been observed in the distal tibia of trainees during Basic Combat Training (BCT), some animal studies have demonstrated greater mechanosensitivity in the juvenile compared to the mature skeleton. How age affects skeletal adaptations to military training is unknown. The purpose of this study was to determine if skeletal adaptations to US Army BCT differ by age. Methods We enrolled 2085 trainees (1303 males, 782 females). High-resolution peripheral quantitative computed tomography was used to assess total, cortical, and trabecular bone mineral density (BMD) and the microarchitecture of the distal tibia before and after 8 wk of BCT. Generalized linear models were used to compare mean percent change (95% confidence interval (CI)) in each bone parameter by age group (<20, 20–25, 26–29, and ≥30 yr) and to evaluate differences in bone parameter changes between age groups (effect estimates (95% CI)). Models were stratified by sex with multivariable adjustment. Results Male and female trainees in all age groups had increases in total BMD, trabecular BMD, and trabecular bone volume fraction from baseline (P < 0.01 for all). Male and female trainees also had increases in trabecular thickness from baseline in all groups (P < 0.05) except females ≥30 yr old. Female trainees 20–25 yr old had a significantly larger increase in trabecular thickness than those <20 yr old (effect estimate (95% CI), 0.33% (0.02%–0.64%); P < 0.05). Trabecular microarchitecture was largely not otherwise different between age groups for either sex. Male and female trainees <20 yr old had greater changes in cortical BMD compared to older age groups (males, P < 0.01; females, P < 0.05 for all). Conclusion Trainees <20 yr old experience the greatest improvements in cortical BMD at the distal tibia during US Army BCT, suggesting that adaptive bone formation in cortical bone may be attenuated with skeletal maturity. However, the mechanosensitivity of trabecular bone to exercise training remains intact regardless of age.

Comparative Analysis of Morphometric, Densitometric, and Mechanical Properties of Skeletal Locomotor Elements in Three Duck Species (Anatidae: Anatinae).

Ducks (Anatinae) play a crucial role in wetland ecosystems, contributing to seed dispersal and nutrient cycling. This study investigates the skeletal adaptations of three duck species: the Mallard (Anas platyrhynchos), Tufted Duck (Aythya fuligula), and Green-Winged Teal (Anas crecca). The focus is on the tibiotarsus and humerus bones to understand how these adaptations support their different locomotion and habitat preferences. Bone samples n = 6 of deceased ducks (both male and female) from each species (for a total of 36 samples) were cleaned and measured for length, weight, and density. Dual-energy X-ray absorptiometry was used to determine bone mineral density (BMD) and bone mineral content (BMC), and mechanical properties like yield force and stiffness were tested using a 3-point bending test. The results show significant differences in body weight, bone weight, and bone length among the species, with Mallards being the largest and Teals the smallest. Male Teals displayed higher relative bone weight (RBW) in their tibia compared to male Mallards, and male Mallards had significantly lower RBW in the humerus compared to the other species. Female Teals had higher RBW than the other species. Teals also exhibited much lower BMD in the tibia, whereas female Mallards had lower BMD in the humerus. The Seedor index revealed that male Mallards had the highest values in the tibia, while female Teals had the lowest. Mechanical testing indicated that Teals had lower yield force and breaking force in the tibia, whereas Mallards showed the highest stiffness in both bones. Tufted Ducks had intermediate values, consistent with their diving behaviour. These findings suggest that the Mallard's robust bones support its adaptability to various environments and diverse locomotion and foraging strategies. The Teal's lighter and less dense bones facilitate rapid flight and agility in shallow wetlands. The Tufted Duck's intermediate bone characteristics reflect its specialization in diving, requiring a balance of strength and flexibility. Understanding these skeletal differences may provide valuable insights into the evolutionary biology and biomechanics of these species, aiding in their conservation and enhancing our knowledge of their roles in wetland ecosystems. By exploring the functional morphology of these ducks, this study aims to shed light on the biomechanical mechanisms that underpin their locomotion and foraging behaviours.

Adaptation of the diaphonization protocol and the highlight of some significant structures development in the chicken embryo (Gallus gallus) skeleton

Diaphonization is a technique used in developmental biology, anatomy, and comparative morphology to visualize and study the internal structures of small organisms. In this study, we used diaphonization to visualize the development of chicken embryos (Gallus gallus). Diaphonization was performed on chicken eggs at different stages of development, from 10 to 13 days of incubation, and the resulting specimens were analyzed using microscopy. The results suggest that for embryos older than 14 days, a longer storage time in 1% KOH is recommended (approximately 30% longer incubation time compared to the original protocol). In the case of more developed chicken embryos, it is also recommended to carry out evisceration. These results provide insight into the early stages of avian development and may have applications in the fields of developmental biology and anatomy. Keywords: diaphonization protocol, chicken embryo development, skeletal visualization, developmental biology, avian skeletal adaptation.

How does the shape of the wing and hindlimb bones of aquatic birds relate to their locomotor abilities?

Aquatic birds represent diverse ecologies and locomotion types. Some became flightless or lost the ability for effective terrestrial locomotion, yet, certain species excel in water, on land, and in air, despite differing physical characteristics associated with each medium. In this exploratory study, we intend to quantitatively analyze the morphological variety of multiple limb bones of aquatic birds using 3D geometric morphometrics. Morphological variation is mainly driven by phylogeny, which also affects size and locomotion. However, the shape of the ulna, including the proportion and orientation of the epiphyses is influenced by size and aquatic propulsive techniques even when phylogeny is taken into consideration. Certain trends, possibly linked to functions, can be observed too in other bones, notably in cases where phylogenetic and functional signals are probably mixed when some taxa only englobe species with similar functional requirements: penguins exhibit the most distinctive wing bone morphologies, highly adapted to wing-propulsion; advanced foot-propellers exhibit femur morphology that reduces proximal mobility but supports stability; knee structures, like cnemial crests of varied sizes and orientations, are crucial for muscle attachments and efficient movement in water and on land; taxa relying on their feet in water but retaining terrestrial abilities share features enabling swimming and walking postures. Size-linked changes distinguish the wing bones of non-wing-propelled taxa. For hindlimbs, larger size relates to robust bones probably linked to terrestrial abilities, but robustness in femora can be connected to foot-propulsion. These results help us better understand birds' skeletal adaptation and can be useful inferring extinct species' ecology.

Gut microbial alterations in arginine metabolism determine bone mechanical adaptation

Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.

Small skeletons show size-specific scaling: an exploration of allometry in the mammalian lumbar spine.

Studies of vertebrate bone biomechanics often focus on skeletal adaptations at upper extremes of body mass, disregarding the importance of skeletal adaptations at lower extremes. Yet mammals are ancestrally small and most modern species have masses under 5 kg, so the evolution of morphology and function at small size should be prioritized for understanding how mammals subsist. We examined allometric scaling of lumbar vertebrae in the small-bodied Philippine endemic rodents known as cloud rats, which vary in mass across two orders of magnitude (15.5 g-2700 g). External vertebral dimensions scale with isometry or positive allometry, likely relating to body size and nuances in quadrupedal posture. In contrast to most mammalian trabecular bone studies, bone volume fraction and trabecular thickness scale with positive allometry and isometry, respectively. It is physiologically impossible for these trends to continue to the upper extremes of mammalian body size, and we demonstrate a fundamental difference in trabecular bone allometry between large- and small-bodied mammals. These findings have important implications for the biomechanical capabilities of mammalian bone at small body size; for the selective pressures that govern skeletal evolution in small mammals; and for the way we define 'small' and 'large' in the context of vertebrate skeletons.

Comparative skeletal anatomy of salt marsh and western harvest mice in relation to locomotor ecology.

The salt marsh harvest mouse (Reithrodontomys raviventris) is an endangered species, endemic to the San Francisco Bay Estuary, that co-occurs with the more broadly distributed species, the western harvest mouse (Reithrodontomys megalotis). Despite their considerable external morphological similarities, the northern subspecies of salt marsh harvest mice have relatively longer and thicker tails than do western harvest mice, which may be related to their abilities to climb emergent marsh vegetation to avoid tidal inundation. We used micro-CT to compare post-cranial skeletal anatomy between the salt marsh and western harvest mouse, to examine whether the salt marsh harvest mouse's restriction to brackish marshes is associated with skeletal adaptations for scansorial locomotion. We found that salt marsh harvest mice exhibited a deeper 3rd caudal vertebra, a more caudally located longest tail vertebra, craniocaudally longer tail vertebrae, and a longer digit III proximal phalanx than western harvest mice. These phalangeal and vertebral characteristics are known to decrease body rotations during climbing, increase contact with substrates, and decrease fall susceptibility in arboreal mammals, suggesting that the salt marsh harvest mouse may be morphologically specialized for scansorial locomotion, adaptive for its dynamic wetland environment.

Comparing lateral plantar process trabecular structure to other regions of the human calcaneus.

Investigating skeletal adaptations to bipedalism informs our understanding of form-function relationships. The calcaneus is an important skeletal element to study because it is a weight-bearing bone with a critical locomotor role. Although other calcaneal regions have been well studied, we lack a clear understanding of the functional role of the lateral plantar process (LPP). The LPP is a bony protuberance on the inferolateral portion of the calcaneus thought to aid the tuberosity in transmission of ground reaction forces during heel-strike. Here, we analyze LPP internal trabecular structure relative to other calcaneal regions to investigate its potential functional affinities. Human calcanei (n = 20) were micro-CT scanned, and weighted spherical harmonic analysis outputs were used to position 251 volumes of interest (VOI) within each bone. Trabecular thickness (Tb.Th), spacing (Tb.Sp), degree of anisotropy (DA), and bone volume fraction (BV/TV) were calculated for each VOI. Similarities in BV/TV and DA (p = 0.2741) between the LPP and inferior tuberosity support suggestions that the LPP is a weight-bearing structure that may transmit forces in a similar direction. The LPP significantly differs from the inferior tuberosity in Tb.Th and Tb.Sp (p < 0.05). Relatively thinner, more closely spaced trabeculae in the LPP may serve to increase internal surface area to compensate for its relatively small size compared to the tuberosity. Significant differences in all parameters between LPP and joint articular surfaces indicate that trabecular morphology is differently adapted for the transmission of forces associated with body mass through joints.

Bipedalism and the dawn of uterine fibroids.

The high prevalence and burden of uterine fibroids in women raises questions about the origin of these benign growths. Here, we propose that fibroids should be understood in the context of human evolution, specifically the advent of bipedal locomotion in the hominin lineage. Over the ≥7 million years since our arboreal ancestors left their trees, skeletal adaptations ensued, affecting the pelvis, limbs, hands, and feet. By 3.2 million years ago, our ancestors were fully bipedal. A key evolutionary advantage of bipedalism was the freedom to use hands to carry and prepare food and create and use tools which, in turn, led to further evolutionary changes such as brain enlargement (encephalization), including a dramatic increase in the size of the neocortex. Pelvic realignment resulted in narrowing and transformation of the birth canal from a simple cylinder to a convoluted structure with misaligned pelvic inlet, mid-pelvis, and pelvic outlet planes. Neonatal head circumference has increased, greatly complicating parturition in early and modern humans, up to and including our own species. To overcome the so-called obstetric dilemma provoked by bipedal locomotion and encephalization, various compensatory adaptations have occurred affecting human neonatal development. These include adaptations limiting neonatal size, namely altricial birth (delivery of infants at an early neurodevelopmental stage, relative to other primates) and mid-gestation skeletal growth deceleration. Another key adaptation was hyperplasia of the myometrium, specifically the neomyometrium (the outer two-thirds of the myometrium, corresponding to 90% of the uterine musculature), allowing the uterus to more forcefully push the baby through the pelvis during a lengthy parturition. We propose that this hyperplasia of smooth muscle tissue set the stage for highly prevalent uterine fibroids. These fibroids are therefore a consequence of the obstetric dilemma and, ultimately, of the evolution of bipedalism in our hominin ancestors.

Loss of the auxiliary α2δ1 voltage-sensitive calcium channel subunit impairs bone formation and anabolic responses to mechanical loading.

Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α2δ1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1, the gene encoding α2δ1. Dual-energy X-ray absorptiometry and microcomputed tomography imaging demonstrated that deletion of α2δ1 diminished bone mineral content and density in both male and female C57BL/6 mice. Structural differences manifested in both trabecular and cortical bone for males, while the absence of α2δ1 affected only cortical bone in female mice. Deletion of α2δ1 impaired skeletal mechanical properties in both sexes, as measured by three-point bending to failure. While no changes in osteoblast number or activity were found for either sex, male mice displayed a significant increase in osteoclast number, accompanied by increased eroded bone surface and upregulation of genes that regulate osteoclast differentiation. Deletion of α2δ1 also rendered the skeleton insensitive to exogenous mechanical loading in males. While previous work demonstrates that VSCCs are essential for anabolic responses to mechanical loading, the mechanism by which these channels sense and respond to force remained unclear. Our data demonstrate that the α2δ1 auxiliary VSCC subunit functions to maintain baseline bone mass and strength through regulation of osteoclast activity and also provides skeletal mechanotransduction in male mice. These data reveal a molecular player in our understanding of the mechanisms by which VSCCs influence skeletal adaptation.

Skeletal adaptation to mechanical cues during homeostasis and repair: the niche, cells, and molecular signaling.

Bones constantly change and adapt to physical stress throughout a person's life. Mechanical signals are important regulators of bone remodeling and repair by activating skeletal stem and progenitor cells (SSPCs) to proliferate and differentiate into bone-forming osteoblasts using molecular signaling mechanisms not yet fully understood. SSPCs reside in a dynamic specialized microenvironment called the niche, where external signals integrate to influence cell maintenance, behavior and fate determination. The nature of the niche in bone, including its cellular and extracellular makeup and regulatory molecular signals, is not completely understood. The mechanisms by which the niche, with all of its components and complexity, is modulated by mechanical signals during homeostasis and repair are virtually unknown. This review summarizes the current view of the cells and signals involved in mechanical adaptation of bone during homeostasis and repair, with an emphasis on identifying novel targets for the prevention and treatment of age-related bone loss and hard-to-heal fractures.

Prolonged cyclical loading induces Haversian remodeling in mandibles of growing rabbits.

Bone adaptation to mechanical loading happens predominantly via modeling and remodeling, but the latter is poorly understood. Haversian remodeling (cortical bone replacement resulting in secondary osteons) is thought to occur in regions of low strain as part of bone maintenance or high strain in response to microdamage. However, analyses of remodeling in primates have revealed an unappreciated association with the number of daily load cycles. We tested this relationship by raising 30 male domestic rabbits (Oryctolagus cuniculus) on disparate diets from weaning to adulthood (48 weeks), facilitating a naturalistic perspective on mandibular bone adaptation. A control group consumed only rabbit pellets and an 'overuse' group ate hay in addition to pellets. To process hay, which is tougher and stiffer, rabbits increase chewing investment and duration without increasing bite force (i.e. corpus mean peak strain is similar for the two foods). Corpus remodeling in overuse rabbits was ∼1.5 times that of controls, measured as osteon population density and percentage Haversian bone. In the same subjects, there was a significant increase in overuse corpus bone formation (ratio of cortical area to cranial length), consistent with previous reports on the same dietary manipulation and bone formation in rabbits. This is the first evidence that both modeling and remodeling are simultaneously driven by the number of load cycles, independent of strain magnitude. This novel finding provides unique data on the feeding apparatus, challenges traditional thought on Haversian remodeling, and highlights the need for experimental studies of skeletal adaptation that examine mechanical factors beyond strain magnitude.

A review of the late Cenozoic genus Bohra (Diprotodontia: Macropodidae) and the evolution of tree-kangaroos.

Tree-kangaroos of the genus Dendrolagus occupy forest habitats of New Guinea and extreme northeastern Australia, but their evolutionary history is poorly known. Descriptions in the 2000s of near-complete Pleistocene skeletons belonging to larger-bodied species in the now-extinct genus Bohra broadened our understanding of morphological variation in the group and have since helped us to identify unassigned fossils in museum collections, as well as to reassign species previously placed in other genera. Here we describe these fossils and analyse tree-kangaroo systematics via comparative osteology. Including B. planei sp. nov., B. bandharr comb. nov. and B. bila comb. nov., we recognise the existence of at least seven late Cenozoic species of Bohra, with a maximum of three in any one assemblage. All tree-kangaroos (Dendrolagina subtribe nov.) exhibit skeletal adaptations reflective of greater joint flexibility and manoeuvrability, particularly in the hindlimb, compared with other macropodids. The Pliocene species of Bohra retained the stepped calcaneocuboid articulation characteristic of ground-dwelling macropodids, but this became smoothed to allow greater hindfoot rotation in the later species of Bohra and in Dendrolagus. Tree-kangaroo diversification may have been tied to the expansion of forest habitats in the early Pliocene. Following the onset of late Pliocene aridity, some tree-kangaroo species took advantage of the consequent spread of more open habitats, becoming among the largest late Cenozoic tree-dwellers on the continent. Arboreal Old World primates and late Quaternary lemurs may be the closest ecological analogues to the species of Bohra.

The Contribution of Perilacunar Composition and Mechanical Properties to Whole-Bone Mechanical Outcomes in Streptozotocin-Induced Diabetes.

Osteocytes are the most abundant cell type in bone and remodel their local perilacunar matrix in response to a variety of stimuli and diseases. How the perilacunar composition and mechanical properties are affected by type 1 diabetes (T1D), and the contribution of these local changes to the decline in whole-bone functional properties that occurs with diabetes remains unclear. 12-14week old C57/BL6 male mice were administered a series of low-dose streptozotocin injections and sacrificed at baseline (BL), 3 (D3) and 7weeks (D7) following confirmation of diabetes, along with age-matched controls (C3, C7). Femora were then subjected to a thorough morphological (μCT), mechanical (four-point bending, nanoindentation), and compositional (HPLC for collagen cross-links, Raman spectroscopy) analysis at the whole-bone and local (perilacunar and intracortical) levels. At the whole-bone level, D7 mice exhibited 10.7% lower ultimate load and 26.4% lower post-yield work relative to C7. These mechanical changes coincided with 52.2% higher levels of pentosidine at D7 compared to C7. At the local level, the creep distance increased, while modulus and hardness decreased in the perilacunar region relative to the intracortical for D7 mice, suggesting a spatial uncoupling in skeletal adaptation. D7 mice also exhibited increased matrix maturity in the 1660/1690cm-1 ratio at both regions relative to C7. The perilacunar matrix maturity was predictive of post-yield work (46%), but perilacunar measures were not predictive of ultimate load, which was better explained by cortical area (26%). These results show that diabetes causes local perilacunar composition perturbations that affect whole-bone level mechanical properties, implicating osteocyte maintenance of its local matrix in the progression of diabetic skeletal fragility.

Burrows provided shelter for tetrapods in a Permo‐Triassic desert

AbstractWe describe for the first time the presence of straight, curved and quasi‐helical burrows preserved in plan, oblique and transversal views in the aeolian strata of the Permo‐Triassic Buena Vista Formation (Paraná Basin), Rio Grande do Sul, southern Brazil. The morphology of the burrows is similar to that of others found in Guadalupian to Early Triassic‐aged deposits in several parts of the world. Of these, middle Permian dicynodont‐bearing helical burrows (Daimonelix) and Early–Middle Triassic kidney‐shaped burrows (Reniformichnus), both from the Karoo Basin of South Africa, show a remarkable similarity to the Brazilian burrows, prompting a discussion of the probable producers. Dicynodonts, cynodonts, therocephalian and/or procolophonians are among the probable producers of such burrows, based on size compatibility between the burrows and estimates of body size for the fossil taxa, along with the presence of skeletal adaptations in Permo‐Triassic tetrapods for digging (bone micro‐ and macrostructure). Last, we discuss some behavioural aspects of the producer of the burrows, mainly due to the presence of passive filling and bilobate bottoms in the tunnels, which indicates that they remained open as long as they were occupied. The burrows were excavated in a dry aeolian system that occurred in the Guadalupian–Induan interval of Brazil, representing the oldest unambiguous record of tetrapod dwelling structures in such an environment, and providing new and unprecedented information regarding the colonization of deserts by tetrapods during the end‐Permian biotic crisis.

Toll-like receptor 4 signaling in osteoblasts is required for load-induced bone formation in mice

In mature bone, NGF is produced by osteoblasts following mechanical loading and signals through resident sensory nerves expressing its high affinity receptor, neurotrophic tyrosine kinase receptor type 1 (TrkA), to support bone formation. Here, we investigated whether osteoblastic expression of Toll-like receptor 4 (TLR4), a key receptor in the NF-κB signaling pathway, is required to initiate NGF-TrkA signaling required for load-induced bone formation. Although Tlr4 conditional knockout mice have normal skeletal mass and strength in adulthood, the loss of TLR4 signaling significantly reduced lamellar bone formation following loading. Inhibition of TLR4 signaling reduced Ngf expression in primary osteoblasts and RNA sequencing of bones from Tlr4 conditional knockout mice and wild-type littermates revealed dysregulated inflammatory signaling three days after osteogenic mechanical loading. In total, our study reveals an important role for osteoblastic TLR4 in the skeletal adaptation of bone to mechanical forces.