Scale-based landmark for internal organs assessments of common carp (Cyprinus carpio) during digital radiography and ultrasonography imaging.

Medical imaging techniques such as digital radiography and ultrasonography are non-invasive and provide precise results for examining internal organs and structures within fish. Their effectiveness can be further enhanced by using body parts like scales as markers for the organs beneath them. This study utilized the number of scales as landmarks in digital radiography and ultrasonography to non-invasively evaluate the muscles, bones, and images of internal and reproductive organs of common carp (Cyprinus carpio). Digital radiography was performed in the dorsoventral and lateral views of the fish, whereas ultrasonography was conducted in longitudinal and transverse views on sequence scale numbers with brightness and colour Doppler-modes. Digital radiography of the common carp revealed the whole-body morphology, including the bony parts from the head, pectoral fins, dorsal fins, pelvic fins, anal fins, and vertebrae to the tail that appeared radiopaque. Internal organs were also observed, with the swim bladder and heart appeared radiolucent, while the intestines, liver, testes, and ovaries appeared radiopaque. Ultrasonography in brightness mode displayed the digestive organs, reproductive organs, and muscle thickness. Additionally, colour Doppler mode demonstrated blood flow within the heart's ventricle.

The Interplay of Lipid Signaling in Musculoskeletal Cross Talk: Implications for Health and Disease.

The intricate interplay between the muscle and bone tissues is a fundamental aspect of musculoskeletal physiology. Over the past decades, emerging research has highlighted the pivotal role of lipid signaling in mediating communication between these tissues. This chapter delves into the multifaceted mechanisms through which lipids, particularly phospholipids, sphingolipids, and eicosanoids, participate in orchestrating cellular responses and metabolic pathways in both muscle and bone. Additionally, we examine the clinical implications of disrupted lipid signaling in musculoskeletal disorders, offering insights into potential therapeutic avenues. This chapter aims to shed light on the complex lipid-driven interactions between the muscle and bone tissues, paving the way for a deeper understanding of musculoskeletal health and disease.

Sedimentary biomarkers and bone specimens reveal a history of prehistoric occupation on Somerset Island (Arctic Canada).

Archaeological studies of pre-historic Arctic cultures are often limited to artefacts and architecture; such records may be incomplete and often do not provide a continuous record of past occupation. Here, we used lake sediment archives to supplement archaeological evidence to explore the history of Thule and Dorset populations on Somerset Island, Nunavut (Canada). We examined biomarkers in dated sediment cores from two ponds adjacent to abandoned Thule settlements (PaJs-3 and PaJs-13) and compared these to sediment cores from two ponds without past human occupation. Coprostanol and epicoprostanol, δ15N measurements, sedimentary chlorophyll a and the ratio of diatom valves to chrysophyte cysts were elevated in the dated sediment profiles at both sites during Thule and Dorset occupations. Periods of pronounced human impact during the Thule occupation of the site were corroborated by 14C-dated caribou bones found at both sites that identified intense caribou hunting between ca 1185 and 1510 CE. Notably, these sediment core data show evidence of the Dorset occupation from ca 200 to 500 CE at sites where archaeological evidence was heretofore lacking. We highlight the utility of lake sediments in assisting archaeological studies to better establish the timings, peak occupations and even lifestyle practices of the Dorset and Thule Arctic peoples.

PCLAF induces bone marrow adipocyte senescence and contributes to skeletal aging.

Bone marrow adipocytes (BMAds) affect bone homeostasis, but the mechanism remains unclear. Here, we showed that exercise inhibited PCNA clamp-associated factor (PCLAF) secretion from the bone marrow macrophages to inhibit BMAds senescence and thus alleviated skeletal aging. The genetic deletion of PCLAF in macrophages inhibited BMAds senescence and delayed skeletal aging. In contrast, the transplantation of PCLAF-mediated senescent BMAds into the bone marrow of healthy mice suppressed bone turnover. Mechanistically, PCLAF bound to the ADGRL2 receptor to inhibit AKT/mTOR signaling that triggered BMAds senescence and subsequently spread senescence among osteogenic and osteoclastic cells. Of note, we developed a PCLAF-neutralizing antibody and showed its therapeutic effects on skeletal health in old mice. Together, these findings identify PCLAF as an inducer of BMAds senescence and provide a promising way to treat age-related osteoporosis.

Bone Morphogenetic Protein 7-Loaded Gelatin Methacrylate/Oxidized Sodium Alginate/Nano-Hydroxyapatite Composite Hydrogel for Bone Tissue Engineering.

Background: Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration. Methods: Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models. Results: The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups. Conclusion: Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.

The expression of MIR125B transcripts and bone phenotypes in Mir125b2-deficient mice.

MIR125B, particularly its 5p strand, is apparently involved in multiple cellular processes, including osteoblastogenesis and osteoclastogenesis. Given that MIR125B is transcribed from the loci Mir125b1 and Mir125b2, three mature transcripts (MIR125B-5p, MIR125B1-3p, and MIR125B2-3p) are generated (MIR125B-5p is common to both); however, their expression profiles and roles in the bones remain poorly understood. Both primary and mature MIR125B transcripts were differentially expressed in various organs, tissues, and cells, and their expression patterns did not necessarily correlate in wild-type (WT) mice. We generated Mir125b2 knockout (KO) mice to examine the contribution of Mir125b2 to MIR125B expression profiles and bone phenotypes. Mir125b2 KO mice were born and grew normally without any changes in bone parameters. Interestingly, in WT and Mir125b2 KO, MIR125B-5p was abundant in the calvaria and bone marrow stromal cells. These results indicate that the genetic ablation of Mir125b2 does not impinge on the bones of mice, attracting greater attention to MIR125B-5p derived from Mir125b1. Future studies should investigate the conditional deletion of Mir125b1 and both Mir125b1 and Mir125b2 in mice.

Comparative Analysis of Myokines and Bone Metabolism Markers in Prepubertal Vegetarian and Omnivorous Children.

The role of bone and muscle as endocrine organs may be important contributing factors for children's growth and development. Myokines, secreted by muscle cells, play a role in regulating bone metabolism, either directly or indirectly. Conversely, markers of bone metabolism, reflecting the balance between bone formation and bone resorption, can also influence myokine secretion. This study investigated a panel of serum myokines and their relationships with bone metabolism markers in children following vegetarian and omnivorous diets. A cohort of sixty-eight healthy prepubertal children, comprising 44 vegetarians and 24 omnivores, participated in this study. Anthropometric measurements, dietary assessments, and biochemical analyses were conducted. To evaluate the serum concentrations of bone markers and myokines, an enzyme-linked immunosorbent assay (ELISA) was used. The studied children did not differ regarding their serum myokine levels, except for a higher concentration of decorin in the vegetarian group (p = 0.020). The vegetarians demonstrated distinct pattern of bone metabolism markers compared to the omnivores, with lower levels of N-terminal propeptide of type I procollagen (P1NP) (p = 0.001) and elevated levels of C-terminal telopeptide of type I collagen (CTX-I) (p = 0.018). Consequently, the P1NP/CTX-I ratio was significantly decreased in the vegetarians. The children following a vegetarian diet showed impaired bone metabolism with reduced bone formation and increased bone resorption. Higher levels of decorin, a myokine involved in collagen fibrillogenesis and essential for tissue structure and function, may suggest a potential compensatory mechanism contributing to maintaining bone homeostasis in vegetarians. The observed significant positive correlations between myostatin and bone metabolism markers, including P1NP and soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), suggest an interplay between muscle and bone metabolism, potentially through the RANK/RANKL/OPG signaling pathway.

Development of Bioactive Hybrid Poly(lactic acid)/Poly(methyl methacrylate) (PLA/PMMA) Electrospun Fibers Functionalized with Bioglass Nanoparticles for Bone Tissue Engineering Applications.

Hybrid scaffolds that are based on PLA and PLA/PMMA with 75/25, 50/50, and 25/75 weight ratios and functionalized with 10 wt.% of bioglass nanoparticles (n-BG) were developed using an electrospinning technique with a chloroform/dimethylformamide mixture in a 9:1 ratio for bone tissue engineering applications. Neat PLA and PLA/PMMA hybrid scaffolds were developed successfully through a (CF/DMF) solvent system, obtaining a random fiber deposition that generated a porous structure with pore interconnectivity. However, with the solvent system used, it was not possible to generate fibers in the case of the neat PMMA sample. With the increase in the amount of PMMA in PLA/PMMA ratios, the fiber diameter of hybrid scaffolds decreases, and the defects (beads) in the fiber structure increase; these beads are associated with a nanoparticle agglomeration, that could be related to a low interaction between n-BG and the polymer matrix. The Young's modulus of PLA/PMMA/n-BG decreases by 34 and 80%, indicating more flexible behavior compared to neat PLA. The PLA/PMMA/n-BG scaffolds showed a bioactive property related to the presence of hydroxyapatite crystals in the fiber surface after 28 days of immersion in a Simulated Body Fluids solution (SBF). In addition, the hydrolytic degradation process of PLA/PMMA/n-BG, analyzed after 35 days of immersion in a phosphate-buffered saline solution (PBS), was less than that of the pure PLA. The in vitro analysis using an HBOF-1.19 cell line indicated that the PLA/PMMA/n-BG scaffold showed good cell viability and was able to promote cell proliferation after 7 days. On the other hand, the in vivo biocompatibility evaluated via a subdermal model in BALC male mice corroborated the good behavior of the scaffolds in avoiding the generation of a cytotoxic effect and being able to enhance the healing process, suggesting that the materials are suitable for potential applications in tissue engineering.

Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions.

Advancing age is associated with several age-related diseases (ARDs), with musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic conditions contributing towards considerable number of patients, a deeper understanding of bone aging is the need of the hour. One of the underlying factors of bone aging is cellular senescence and its associated senescence associated secretory phenotype (SASP). SASP comprises of pro-inflammatory markers, cytokines and chemokines that arrest cell growth and development. The accumulation of SASP over several years leads to chronic low-grade inflammation with advancing age, also known as inflammaging. The pathways and molecular mechanisms focused on bone senescence and inflammaging are currently limited but are increasingly being explored. Most of the genes, pathways and mechanisms involved in senescence and inflammaging coincide with those associated with cancer and other ARDs like osteoarthritis (OA). Thus, exploring these pathways using techniques like sequencing, identifying these factors and combatting them with the most suitable approach are crucial for healthy aging and the early detection of ARDs. Several approaches can be used to aid regeneration and reduce senescence in the bone. These may be pharmacological, non-pharmacological and lifestyle interventions. With increasing evidence towards the intricate relationship between aging, senescence, inflammation and ARDs, these approaches may also be used as anti-aging strategies for the aging bone marrow (BM).

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

Evaluation of Different Subperiosteal Implant Thicknesses on Mechanical Strength and Stress on Bone by Finite Element Analysis.

Implants have always been within the interest of both clinicians and material scientists due to their places in reconstructive and prosthetics surgery. Excessive bone loss or resorption in some patients makes it difficult to design and manufacture the implants that bear the necessary loads to carry the final prosthetics. With this study; we tried to determine the minimum material thickness of the subperiosteal implants that can withstand the physiological forces. We have created a digital average bone structure based on actual patient data and designed different subperiosteal implants with 1, 1.5, and 2mm material thicknesses (M1, M2, M3) for this digital model. The designed implant models are subjected to 250 Newtons (N) of force, and the implant and bone are tested for the stress they are exposed to, the pressure they transmit to, and their mechanical strength with Finite Element Analysis with the physical parameters boot for the implant material and human bone. Results show us that under specific design parameters and thicknesses, the 1mm thickness design failed due to exceeding the yield stress limit of 415MPa with a 495,44MPa value. The thinnest implant showed plastic deformation and transmitted excessive forces, which may cause bone resorption due to residual stress. We determined that thinner subperiosteal implants down to 1.5mm that have the necessary material parameters for function and tissue support can be designed and manufactured with current technologies.

Diverse growth rates in Triassic archosaurs-insights from a small terrestrial Middle Triassic pseudosuchian.

The small pseudosuchian Benggwigwishingasuchus eremacarminis was found in Anisian (Middle Triassic) marine sediments. Neither the skeleton nor osteohistology or microanatomy shows any secondary aquatic adaptations, and a dominantly terrestrial lifestyle of this new taxon is evident. Bone tissue consists of a scaffold of parallel-fibered matrix, which is moderately vascularized by small, mainly longitudinal primary osteons. The innermost cortex is less densely vascularized and more highly organized. No parts of the cortex contain any woven bone. The cortex is regularly stratified by annual growth marks. Bone tissue and growth pattern indicate an adult individual that has had slow growth rates throughout its ontogeny. Tissue type, slow growth rate, and inferred low resting metabolic rate of Benggwigwishingasuchus are similar to that of crocodylomorphs but differ from that of Sillosuchus and Effigia, poposaurids to which Benggwigwishingasuchus is related based on phylogenetic analyses. However, according to current knowledge, growth rates in early archosaurs are more likely influenced by body size and environment than by phylogeny. Benggwigwishingasuchus is thus another example of unpredictable variability in growth rates within Triassic archosaurs.

Fabricating vascularized, anatomically accurate bone grafts using 3D bioprinted sectional bone modules, in-situ angiogenesis, BMP-2 controlled release, and bioassembly.

Bone grafting is the most common treatment for repairing bone defects. However, current bone grafting methods have several drawbacks. Bone tissue engineering emerges as a promising solution to these problems. An ideal engineered bone graft should exhibit high mechanical strength, osteogenic properties, and pre-vascularization. Both top-down (using bulk scaffold) and bottom-up (using granular modules) approaches face challenges in fulfilling these requirements. In this paper, we propose a novel sectional modular bone approach to construct osteogenic, pre-vascularized bone grafts in anatomical shapes. We 3D-printed a series of rigid, thin, sectional, porous scaffolds from a biodegradable polymer, tailored to the dimensions of a femur bone shaft. These thin sectional modules promote efficient nutrition and waste removal due to a shorter diffusion distance. The modules were pre-vascularized viain-situangiogenesis, achieved through endothelial cell sprouting from the scaffold struts. Angiogenesis was further enhanced through co-culture with bioprinted fibroblast microtissues, which secreted pre-angiogenic growth factors. Sectional modules were assembled around a porous rod incorporated with Bone Morphogenetic Protein-2 (BMP-2), which released over 3 weeks, demonstrating sustained osteogenic activity. The assembled scaffold, in the anatomical shape of a human femur shaft, was pre-vascularized, osteogenic, and possessed high mechanical strength, supporting 12 times the average body weight. The feasibility of implanting the assembled bone graft was demonstrated using a 3D-printed femur bone defect model. Our method provides a novel modular engineering approach for regenerating tissues that require high mechanical strength and vascularization.

Bone or Tooth dentin: The TGF-ß signaling is the key.

To investigate the cell linkage between tooth dentin and bones, we studied TGF-ß roles during postnatal dentin development using TGF-ß receptor 2 (Tgfßr2) cKO models and cell lineage tracing approaches. Micro-CT showed that the early Tgfßr2 cKO exhibit short roots and thin root dentin (n = 4; p<0.01), a switch from multilayer pre-odontoblasts/odontoblasts to a single-layer of bone-like cells with a significant loss of ~85% of dentinal tubules (n = 4; p<0.01), and a matrix shift from dentin to bone. Mechanistic studies revealed a statistically significant decrease in odontogenic markers, and a sharp increase in bone markers. The late Tgfßr2 cKO teeth displayed losses of odontoblast polarity, a significant reduction in crown dentin volume, and the onset of massive bone-like structures in the crown pulp with high expression levels of bone markers and low levels of dentin markers. We thus concluded that bones and tooth dentin are in the same evolutionary linkage in which TGF-ß signaling defines the odontogenic fate of dental mesenchymal cells and odontoblasts. This finding also raises the possibility of switching the pulp odontogenic to the osteogenic feature of pulp cells via a local manipulation of gene programs in future treatment of tooth fractures.

Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies.

Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

An atlas of brain-bone sympathetic neural circuits in mice.

There is clear evidence that the sympathetic nervous system (SNS) mediates bone metabolism. Histological studies show abundant SNS innervation of the periosteum and bone marrow-these nerves consist of noradrenergic fibers that immunostain for tyrosine hydroxylase, dopamine beta-hydroxylase, or neuropeptide Y. Nonetheless, the brain sites that send efferent SNS outflow to the bone have not yet been characterized. Using pseudorabies (PRV) viral transneuronal tracing, we report, for the first time, the identification of central SNS outflow sites that innervate bone. We find that the central SNS outflow to bone originates from 87 brain nuclei, sub-nuclei, and regions of six brain divisions, namely the midbrain and pons, hypothalamus, hindbrain medulla, forebrain, cerebral cortex, and thalamus. We also find that certain sites, such as the raphe magnus (RMg) of the medulla and periaqueductal gray (PAG) of the midbrain, display greater degrees of PRV152 infection, suggesting that there is considerable site-specific variation in the levels of central SNS outflow to the bone. This comprehensive compendium illustrating the central coding and control of SNS efferent signals to bone should allow for a greater understanding of the neural regulation of bone metabolism, and importantly and of clinical relevance, mechanisms for central bone pain.

Bone Marrow Adipose Tissue as a Critical Regulator of Postmenopausal Osteoporosis - A Concise Review.

Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.

Combining traceological analysis and ZooMS on Early Neolithic bone artefacts from the cave of Coro Trasito, NE Iberian Peninsula: Cervidae used equally to Caprinae.

Few studies have combined the analysis of use-wear traces, traceology, and the proteomic taxonomic identification method Zooarchaeology by Mass Spectrometry (ZooMS). Traceology provides information on the usage, in this case, of bone artefacts, while ZooMS allows for taxonomic identifications where diagnostic features are otherwise gone. The approaches therefore offer complementary information on bone artefacts, allowing for insights into species selection strategies in bone tool manufacture and their subsequent use. Here we present a case study of 20 bone artefacts, mainly bone points, from the Early Neolithic cave site of Coro Trasito located on the southern slope of the Central Pyrenees. Hitherto, studies on Early Neolithic bone artefacts from the Iberian Peninsula have suggested based on morphological assessments that Ovis aries/Capra hircus constituted the majority of the bone material selected for bone tool production. However, the taxonomic identification in this study suggests that, at this site, Cervidae was selected equally to that of O. aries/C. hircus. Furthermore, bone artefacts made from Cervidae specimens seem to be utilised in a wider range of artefact types compared to O. aries/C. hircus. Coro Trasito's bone artefact species composition is probably site-specific to some degree, however, morphological assessments of bone artefacts might not be representative and could be biased towards certain species. Therefore, research on bone artefacts' usage could possibly gain new insights by implementing ZooMS in combination with traceology.

Updates in the skeletal and joint protective effects of tocotrienol: a mini review.

Osteoporosis and osteoarthritis continue to pose significant challenges to the aging population, with limited preventive options and pharmacological treatments often accompanied by side effects. Amidst ongoing efforts to discover new therapeutic agents, tocotrienols (TTs) have emerged as potential candidates. Derived from annatto bean and palm oil, TTs have demonstrated efficacy in improving skeletal and joint health in numerous animal models of bone loss and osteoarthritis. Mechanistic studies suggest that TTs exert their effects through antioxidant, anti-inflammatory, Wnt-suppressive, and mevalonate-modulating mechanisms in bone, as well as through self-repair mechanisms in chondrocytes. However, human clinical trials in this field remain scarce. In conclusion, TTs hold promise as agents for preventing osteoporosis and osteoarthritis, pending further evidence from human clinical trials.

Advances in Bone Biology.

Bone is a unique type of mineralised connective tissue that can support and protect soft tissues, contain bone marrow, and allow movement [...].