Air Pollution and Osteoporosis.

Purpose Of Review: The purpose of this review is to provide a background of osteoporosis and air pollution, discussing increasing incidence of the disease with exposure to pollutants and the role that inflammation may play in this process.

Recent Findings: Osteoporosis-related fractures are one of the most pressing challenges for the ageing global population, with significant increases in mortality known to occur after major osteoporotic fractures in the elderly population. Recent studies have established a firm correlative link between areas of high air pollution and increased risk of osteoporosis, particularly alarming given the increasingly urban global population.

Analytical and computational studies predict negligible risk of cell death from eddy generation off flat surfaces in cell culture flow systems.

Cell-based therapies represent the current frontier of biomedical innovations, with the technologies required underpinning treatments as broad as CAR-T cell therapies, stem cell treatments, genetic therapies and mRNA manufacture. A key bottleneck in the manufacturing process for each of these lies in the expansion of cells within a bioreactor vessel, requiring by far the greatest share of time for what are often time-critical therapies. While various designs, culture feeding and mixing methods are employed in these bioreactors, a common concern among manufacturers and researchers lies in whether shear stresses generated by culture media flow will damage cells and inhibit expansion.

Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells' Escape from the Bone Marrow Microenvironment.

Recent therapeutic advancements have markedly increased the survival rates of individuals with multiple myeloma (MM), doubling survival compared to pre-2000 estimates. This progress, driven by highly effective novel agents, suggests a growing population of MM survivors exceeding the 10-year mark post-diagnosis. However, contemporary clinical observations indicate potential trends toward more aggressive relapse phenotypes, characterized by extramedullary disease and dominant proliferative clones, despite these highly effective treatments.

Role of the osteocyte in bone metastasis - The importance of networking.

Metastatic bone disease is a complex condition resulting from the migration and colonization of cancer cells from their primary site to the bone microenvironment, where they typically develop a metastatic niche. Osteocytes, the most abundant cells in bone tissue and the master regulators of bone remodelling, are increasingly thought to play a crucial role in this process through intricate interactions with cancer cells. This review covers the recent progress made in exploring the multifaceted interactions between osteocytes and cancer cells in the metastatic microenvironment, highlighting the importance of signalling networks in bone metastases.

Deep learning models to map osteocyte networks can successfully distinguish between young and aged bone.

Osteocytes, the most abundant and mechanosensitive cells in bone tissue, play a pivotal role in bone homeostasis and mechano-responsiveness, orchestrating the intricate balance between bone formation and resorption under daily activity. Studying osteocyte connectivity and understanding their intricate arrangement within the lacunar canalicular network (LCN) is essential for unraveling bone physiology. This is particularly true as our bones age, which is associated with decreased integrity of the osteocyte network, disrupted mass transport, and lower sensitivity to the mechanical stimuli that allow the skeleton to adapt to changing demands.

A Novel Primary Cilium-Mediated Mechanism Through which Osteocytes Regulate Metastatic Behavior of Both Breast and Prostate Cancer Cells.

Bone metastases are a common cause of suffering in breast and prostate cancer patients, however, the interaction between bone cells and cancer cells is poorly understood. Using a series of co-culture, conditioned media, human cancer spheroid, and organ-on-a-chip experiments, this study reveals that osteocytes suppress cancer cell proliferation and increase migration via tumor necrosis factor alpha (TNF-α) secretion. This action is regulated by osteocyte primary cilia and associated intraflagellar transport protein 88 (IFT88).

Osteocytes and Primary Cilia.

Purpose Of Review: The purpose of this review is to provide a background on osteocytes and the primary cilium, discussing the role it plays in osteocyte mechanosensing.

Recent Findings: Osteocytes are thought to be the primary mechanosensing cells in bone tissue, regulating bone adaptation in response to exercise, with the primary cilium suggested to be a key mechanosensing mechanism in bone. More recent work has suggested that, rather than being direct mechanosensors themselves, primary cilia in bone may instead form a key chemo-signalling nexus for processing mechanoregulated signalling pathways.

In silico assessment of the bone regeneration potential of complex porous scaffolds.

Mechanical environment plays a crucial role in regulating bone regeneration in bone defects. Assessing the mechanobiological behavior of patient-specific orthopedic scaffolds in-silico could help guide optimal scaffold designs, as well as intra- and post-operative strategies to enhance bone regeneration and improve implant longevity. Additively manufactured porous scaffolds, and specifically triply periodic minimal surfaces (TPMS), have shown promising structural properties to act as bone substitutes, yet their ability to induce mechanobiologially-driven bone regeneration has not been elucidated.

Osteoclastogenesis Requires Primary Cilia Disassembly and Can Be Inhibited by Promoting Primary Cilia Formation Pharmacologically.

The primary cilium is a solitary, sensory organelle with many roles in bone development, maintenance, and function. In the osteogenic cell lineage, including skeletal stem cells, osteoblasts, and osteocytes, the primary cilium plays a vital role in the regulation of bone formation, and this has made it a promising pharmaceutical target to maintain bone health. While the role of the primary cilium in the osteogenic cell lineage has been increasingly characterized, little is known about the potential impact of targeting the cilium in relation to osteoclasts, a hematopoietic cell responsible for bone resorption.

Organ-on-a-Chip and Microfluidic Platforms for Oncology in the UK.

Organ-on-chip systems are capable of replicating complex tissue structures and physiological phenomena. The fine control of biochemical and biomechanical cues within these microphysiological systems provides opportunities for cancer researchers to build complex models of the tumour microenvironment. Interest in applying organ chips to investigate mechanisms such as metastatsis and to test therapeutics has grown rapidly, and this review draws together the published research using these microfluidic platforms to study cancer.

Mechanical Stimulation Modulates Osteocyte Regulation of Cancer Cell Phenotype.

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells enter a mechanical microenvironment that is substantially different to that of the primary tumour and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate healthy bone remodelling in response to physical exercise.

Disrupted osteocyte connectivity and pericellular fluid flow in bone with aging and defective TGF-β signaling.

Skeletal fragility in the elderly does not simply result from a loss of bone mass. However, the mechanisms underlying the concurrent decline in bone mass, quality, and mechanosensitivity with age remain unclear. The important role of osteocytes in these processes and the age-related degeneration of the intricate lacunocanalicular network (LCN) in which osteocytes reside point to a primary role for osteocytes in bone aging.

Altered biomechanical stimulation of the developing hip joint in presence of hip dysplasia risk factors.

Fetal kicking and movements generate biomechanical stimulation in the fetal skeleton, which is important for prenatal musculoskeletal development, particularly joint shape. Developmental dysplasia of the hip (DDH) is the most common joint shape abnormality at birth, with many risk factors for the condition being associated with restricted fetal movement. In this study, we investigate the biomechanics of fetal movements in such situations, namely fetal breech position, oligohydramnios and primiparity (firstborn pregnancy).

Stresses and strains on the human fetal skeleton during development.

Mechanical forces generated by fetal kicks and movements result in stimulation of the fetal skeleton in the form of stress and strain. This stimulation is known to be critical for prenatal musculoskeletal development; indeed, abnormal or absent movements have been implicated in multiple congenital disorders. However, the mechanical stress and strain experienced by the developing human skeleton have never before been characterized.

Function and failure of the fetal membrane: Modelling the mechanics of the chorion and amnion.

The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally.

Ontogeny of the Human Pelvis.

The human pelvis has evolved over time into a remarkable structure, optimised into an intricate architecture that transfers the entire load of the upper body into the lower limbs, while also facilitating bipedal movement. The pelvic girdle is composed of two hip bones, os coxae, themselves each formed from the gradual fusion of the ischium, ilium and pubis bones. Unlike the development of the classical long bones, a complex timeline of events must occur in order for the pelvis to arise from the embryonic limb buds.

In silico bone mechanobiology: modeling a multifaceted biological system.

Mechanobiology, the study of the influence of mechanical loads on biological processes through signaling to cells, is fundamental to the inherent ability of bone tissue to adapt its structure in response to mechanical stimulation. The immense contribution of computational modeling to the nascent field of bone mechanobiology is indisputable, having aided in the interpretation of experimental findings and identified new avenues of inquiry. Indeed, advances in computational modeling have spurred the development of this field, shedding new light on problems ranging from the mechanical response to loading by individual cells to tissue differentiation during events such as fracture healing.

Mechanisms of osteocyte stimulation in osteoporosis.

Experimental studies have shown that primary osteoporosis caused by oestrogen-deficiency results in localised alterations in bone tissue properties and mineral composition. Additionally, changes to the lacunar-canalicular architecture surrounding the mechanosensitive osteocyte have been observed in animal models of the disease. Recently, it has also been demonstrated that the mechanical stimulation sensed by osteocytes changes significantly during osteoporosis.

Modeling the biomechanics of fetal movements.

Fetal movements in the uterus are a natural part of development and are known to play an important role in normal musculoskeletal development. However, very little is known about the biomechanical stimuli that arise during movements in utero, despite these stimuli being crucial to normal bone and joint formation. Therefore, the objective of this study was to create a series of computational steps by which the forces generated during a kick in utero could be predicted from clinically observed fetal movements using novel cine-MRI data of three fetuses, aged 20-22 weeks.

Altered mechanical environment of bone cells in an animal model of short- and long-term osteoporosis.

Alterations in bone tissue composition during osteoporosis likely disrupt the mechanical environment of bone cells and may thereby initiate a mechanobiological response. It has proved challenging to characterize the mechanical environment of bone cells in vivo, and the mechanical environment of osteoporotic bone cells is not known. The objective of this research is to characterize the local mechanical environment of osteocytes and osteoblasts from healthy and osteoporotic bone in a rat model of osteoporosis.

Are all osteocytes equal? Multiscale modelling of cortical bone to characterise the mechanical stimulation of osteocytes.

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. This process is orchestrated by a network of mechanosensitive osteocytes that respond to external mechanical signals and recruit osteoblasts and osteoclasts to alter bone mass to meet loading demands. Because of the irregular hierarchical microarchitecture of bone tissue, the precise mechanical stimuli experienced by osteocytes located in different regions of the tissue is not well-understood.

Fluid flow in the osteocyte mechanical environment: a fluid-structure interaction approach.

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading.

Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes.

The osteocyte is believed to act as the main sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on our bones throughout life. However, the precise mechanical stimuli that bone cells experience in vivo are not yet fully understood. The objective of this study is to use computational methods to predict the loading conditions experienced by osteocytes during normal physiological activities.