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Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.

Virtual reality (VR) is a technology that is gaining traction in the consumer market. With it comes an unprecedented ability to track body motions. These body motions are diagnostic of personal identity, medical conditions, and mental states. Previous work has focused on the identifiability of body motions in idealized situations in which some action is chosen by the study designer. In contrast, our work tests the identifiability of users under typical VR viewing circumstances, with no specially designed identifying task. Out of a pool of 511 participants, the system identifies 95% of users correctly when trained on less than 5 min of tracking data per person. We argue these results show nonverbal data should be understood by the public and by researchers as personally identifying data.

Bone remodeling is a lifelong process that gives rise to a mature, dynamic bone structure via a balance between bone formation by osteoblasts and resorption by osteoclasts. These opposite processes allow the accommodation of bones to dynamic mechanical forces, altering bone mass in response to changing conditions. Mechanical forces are indispensable for bone homeostasis; skeletal formation, resorption, and adaptation are dependent on mechanical signals, and loss of mechanical stimulation can therefore significantly weaken the bone structure, causing disuse osteoporosis and increasing the risk of fracture. The exact mechanisms by which the body senses and transduces mechanical forces to regulate bone remodeling have long been an active area of study among researchers and clinicians. Such research will lead to a deeper understanding of bone disorders and identify new strategies for skeletal rejuvenation. Here, we will discuss the mechanical properties, mechanosensitive cell populations, and mechanotransducive signaling pathways of the skeletal system.

The bone matrix plays an indispensable role in the human body, and its unique biomechanical and mechanobiological properties have received much attention. The bone matrix has unique mechanical anisotropy and exhibits both strong toughness and high strength. These mechanical properties are closely associated with human life activities and correspond to the function of bone in the human body. None of the mechanical properties exhibited by the bone matrix is independent of its composition and structure. Studies on the biomechanics of the bone matrix can provide a reference for the preparation of more applicable bone substitute implants, bone biomimetic materials and scaffolds for bone tissue repair in humans, as well as for biomimetic applications in other fields. In providing mechanical support to the human body, bone is constantly exposed to mechanical stimuli. Through the study of the mechanobiology of the bone matrix, the response mechanism of the bone matrix to its surrounding mechanical environment can be elucidated and used for the health maintenance of bone tissue and defect regeneration. This paper summarizes the biomechanical properties of the bone matrix and their biological significance, discusses the compositional and structural basis by which the bone matrix is capable of exhibiting these mechanical properties, and studies the effects of mechanical stimuli, especially fluid shear stress, on the components of the bone matrix, cells and their interactions. The problems that occur with regard to the biomechanics and mechanobiology of the bone matrix and the corresponding challenges that may need to be faced in the future are also described.

Nowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated. We were aiming to summarize the evidences regarding the mechanisms of OTM. Firstly, we introduced the research models as a basis for further discussion of mechanisms. Secondly, we proposed a new hypothesis regarding the primary roles of periodontal ligament cells (PDLCs) and osteocytes involved in OTM mechanisms and summarized the biomechanical and biological responses of the periodontium in OTM through four steps, basically in OTM temporal sequences, as follows: (1) Extracellular mechanobiology of periodontium: biological, mechanical, and material changes of acellular components in periodontium under orthodontic forces were introduced. (2) Cell strain: the sensing, transduction, and regulation of mechanical stimuli in PDLCs and osteocytes. (3) Cell activation and differentiation: the activation and differentiation mechanisms of osteoblast and osteoclast, the force-induced sterile inflammation, and the communication networks consisting of sensors and effectors. (4) Tissue remodeling: the remodeling of bone and periodontal ligament (PDL) in the compression side and tension side responding to mechanical stimuli and root resorption. Lastly, we talked about the clinical implications of the updated OTM mechanisms, regarding optimal orthodontic force (OOF), acceleration of OTM, and prevention of root resorption.

Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments. The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells. The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far. The regulation of two family members, Piezo1 and Piezo2, has been reported to have essential functions in mechanosensation and transduction in different organs and tissues. Recently, the predominant contributions of the Piezo family were reported to occur in the skeletal system, especially in bone development and mechano-stimulated bone homeostasis. Here we review current studies focused on the tissue-specific functions of Piezo1 and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell mechanotransduction. In this review, we emphasize the diverse functions of Piezo1 and Piezo2 and related signaling pathways in osteoblast lineage cells and chondrocytes. We also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases.

Wolff’s law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1 -deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblast-osteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis. Mechanical forces induce bone remodeling, but how bone cells sense mechanical signaling is unclear. Here, the authors show that loss of the mechanotransduction channel Piezo1 in osteoblastic cells impairs osteoclast activity via YAP signaling and collagen expression, leading to reduced bone mass and spontaneous fractures.

Running gait patterns have implications for revealing the causes of injuries between higher-mileage runners and low-mileage runners. However, there is limited research on the possible relationships between running gait patterns and weekly running mileages. In recent years, machine learning algorithms have been used for pattern recognition and classification of gait features to emphasize the uniqueness of gait patterns. However, they all have a representative problem of being a black box that often lacks the interpretability of the predicted results of the classifier. Therefore, this study was conducted using a Deep Neural Network (DNN) model and Layer-wise Relevance Propagation (LRP) technology to investigate the differences in running gait patterns between higher-mileage runners and low-mileage runners. It was found that the ankle and knee provide considerable information to recognize gait features, especially in the sagittal and transverse planes. This may be the reason why high-mileage and low-mileage runners have different injury patterns due to their different gait patterns. The early stages of stance are very important in gait pattern recognition because the pattern contains effective information related to gait. The findings of the study noted that LRP completes a feasible interpretation of the predicted results of the model, thus providing more interesting insights and more effective information for analyzing gait patterns.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

It is widely accepted that contraction of skeletal muscle and the heart involves structural changes in actin-containing thin filaments to allow binding of myosin motors from neighbouring thick filaments, thus driving filament sliding; here, X-ray diffraction of single skeletal muscle cells reveals that this thin-filament mechanism can regulate muscle contraction against low load, but high-load contraction requires a second permissive step involving a structural change in the thick filament. A new take on muscle contraction It is thought that for the contraction of skeletal muscle and the heart, structural changes in the actin-containing thin filaments allow the binding of filaments to myosin motors from the neighbouring thick filaments that drives filament sliding. Yet this decades-old concept cannot account for the fact that, in resting muscle, myosin motors cannot bind to the thin filaments. Vincenzo Lombardi and colleagues test the hypothesis that a second permissive step for muscle shortening involves a structural change in the thick filament. Their analysis of single skeletal muscle cells reveals that the accepted thin-filament mechanism, involving a small fraction of constitutively 'ON' myosin motors, can regulate muscle contraction against low load. However, force generation against high load indeed requires change in the structure of the thick filaments, which under low load form an 'OFF' structure. Contraction of both skeletal muscle and the heart is thought to be controlled by a calcium-dependent structural change in the actin-containing thin filaments, which permits the binding of myosin motors from the neighbouring thick filaments to drive filament sliding 1 , 2 , 3 . Here we show by synchrotron small-angle X-ray diffraction of frog ( Rana temporaria ) single skeletal muscle cells that, although the well-known thin-filament mechanism is sufficient for regulation of muscle shortening against low load, force generation against high load requires a second permissive step linked to a change in the structure of the thick filament. The resting (switched ‘OFF’) structure of the thick filament is characterized by helical tracks of myosin motors on the filament surface and a short backbone periodicity 2 , 4 , 5 . This OFF structure is almost completely preserved during low-load shortening, which is driven by a small fraction of constitutively active (switched ‘ON’) myosin motors outside thick-filament control. At higher load, these motors generate sufficient thick-filament stress to trigger the transition to its long-periodicity ON structure, unlocking the major population of motors required for high-load contraction. This concept of the thick filament as a regulatory mechanosensor provides a novel explanation for the dynamic and energetic properties of skeletal muscle. A similar mechanism probably operates in the heart.