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Bone resorption and bone metastasis risk.

Breast cancer tumors have a tendency to metastasize to the bone. After development of a bone metastasis, the median survival time is 40 mont … the direct effects of chemotherapeutic drugs on bone cells-including osteoclasts, osteoblasts, and osteocytes-and through the decrease in circulating estrogen as a result of chemotherapy-induced ovarian dysfunction. Therefore, it is important for future studies to determine the risk of developing bone metastases associated with increasing bone resorption as …

Musculoskeletal Health in the Context of Spinal Cord Injury.

PURPOSE OF REVIEW: This review assembles recent understanding of the profound loss of muscle and bone in spinal cord injury (SCI). It is important to try to understand these changes, and the context in which they occur, because of their impact on the wellbeing of SC-injured individuals, and the urgent need for viable preventative therapies. RECENT FINDINGS: Recent research provides new understanding of the effects of age and systemic factors on the response of bone to loading, of relevance to attempts to provide load therapy for bone in SCI. The rapidly growing dataset describing the biochemi

Osteogenic potential of a chalcone in a critical-size defect in rat calvaria bone.

BACKGROUND: This study describes the bone formation stimulated by the application of a type of chalcone to critical-size defects in rat calvarial bone. MATERIAL AND METHODS: Sixty female Wistar rats were divided into 6 groups of 10 animals per group: control (no treatment), vehicle (vaseline) and the chalcone (1-phenyl-3-(4-chlorophenyl)-2-propen-1-one) suspended in vaseline at 10%. A critical-size defect of 5 mm was prepared using a trephine in the calvarial bone, after which the treatment was applied, in a single dose, according to the experimental group. The samples were evaluated macrosco

rhBMP-6 stimulated osteoprogenitor cells enhance posterolateral spinal fusion in the New Zealand white rabbit.

BACKGROUND CONTEXT: The nonunion rate after posterolateral spinal fusion can be as high as 35%. This has stimulated interest in the development of techniques for enhancing new bone formation, including the addition of bioactive peptides or the use of cell-based therapies, including genetically modified cells. In previous studies we have demonstrated that exposing autologous, marrow-derived osteoprogenitor cells to a recombinant human bone morphogenetic protein-6 (rhBMP-6) containing extracellular matrix induces osteoblastic differentiation, and that these cells are capable of increasing new bo

Mechanotransduction in musculoskeletal mesenchymal tissues: implications for bone, tendon, and cartilage regenerative engineering-a narrative review.

PURPOSE: To integrate evidence on how mechanical signals regulate musculoskeletal connective-tissue biology and how cellular context and loading history shape mechanotransduction and mechanical memory. METHODS: This narrative review synthesized PubMed-indexed evidence on extracellular matrix mechanics, adhesion complexes, the cytoskeleton, nucleus, primary cilia, mechanosensitive ion channels, cell state, and loading history in bone, tendon, ligament, and cartilage. RESULTS: Mechanotransduction is best understood as a coupled extracellular matrix-integrin-cytoskeleton-nucleus continuum rathe

Multimodal imaging and molecular analysis of a 350-year-old purple heron mummy.

The discovery of glacially preserved remains offers a rare and invaluable opportunity to explore long-term tissue preservation, diagenetic alterations, and microbial colonisation. In this study, we examined a 350-year-old glacier mummy of a purple heron (Ardea purpurea) recovered from the Austrian Alps, specifically from the Gurgler Ferner glacier in Tyrol, Austria, at an altitude of 3.004 m in the area of the Hochwildehaus towards Hochwilde and the Annakegele, marking the first documented instance of an avian glacier mummy in this region. A comprehensive multimodal analytical approach was emp

Effect of axial stress-loaded magnesium alloy intramedullary nails on bone fracture healing.

Biodegradable magnesium (Mg) alloys are promising orthopedic implants. However, the synergistic effects of their degradation and physiological loading on fracture healing require further investigation. This study evaluated Mg-Zn-Y-Nd alloy intramedullary (IM) nails in a rat tibiofibular fracture model under 10 N axial loading. A combined approach of finite element analysis (FEA) and in vivo experiments was utilized to assess stress distribution, degradation kinetics and biological response. FEA validated a dynamic load-sharing mechanism, where maximum callus strain decreased from 1530 to 233 μ

Antibacterial polyphenols for osteomyelitis treatment: from antibacterial mechanisms to biomaterial-based delivery.

Osteomyelitis is a refractory infection caused by bacterial invasion of bone tissue. Biofilms, small-colony variants (SCVs), and intracellular persistence enable bacteria to evade immune clearance and antibiotic killing, while sequestra and implant surfaces may act as long-term infection reservoirs. Some pathogens can also invade the osteocyte lacuno-canalicular network, further hindering complete eradication. Meanwhile, persistent inflammation, oxidative stress, and impaired local blood supply aggravate bone destruction and inhibit tissue repair. Therefore, osteomyelitis treatment requires no

Unidirectional porous beta-tricalcium phosphate supports three-dimensional osteogenic differentiation of human iPS cells without surface coating.

Beta-tricalcium phosphate (βTCP) is widely used as a bone graft substitute, but it lacks intrinsic osteogenic cells. Human induced pluripotent stem cells (iPSCs) are a promising cell source for bone regeneration; however, the suitability of clinically available, uncoated βTCP as a scaffold for iPSC osteogenic differentiation remains unclear. We compared interconnected porous and unidirectional porous βTCP combined with either negative-pressure or atmospheric-pressure seeding. Metabolic activity was assessed using a CCK-8 assay, and the selected condition was further evaluated by RT-qPCR, scann

A proinflammatory response and polarized differentiation of stromal elements characterizes the murine myeloma bone marrow niche.

BACKGROUND: The bone marrow (BM) niche contains non-hematopoietic elements including mesenchymal stromal cells (MSC) and bone marrow endothelial cells (BMEC) which provide mechanical support, and control hematopoietic cell growth and differentiation. Although it is known that multiple myeloma (MM) cells interact closely with the BM microenvironment, little is known about the impact of MM on non-hematopoietic niche-forming cells. METHODS: To address the role of the niche in MM pathogenesis, we utilized the 5TGM1 murine model. During the asymptomatic precursor stage of the model, we isolated th

Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

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… Physiology of Bone Remodeling Bone remodeling is a dynamic, tightly regulated process driven by the coordinated actions of osteoblasts, osteoclasts, and osteocytes. … Apoptotic osteocytes—often a consequence of disuse or microdamage—release ATP and other factors that upregulate RANKL in neighboring cells, triggering localized remodeling. …

Combined antiresorptive and new anabolic drug approach in osteogenesis imperfecta zebrafish models.

Osteogenesis imperfecta (OI) is a family of heritable collagen I-related skeletal disorders for which, to date, no definitive cure is available. Individuals with OI are mainly treated with bisphosphonates that enhance bone mass by inhibiting bone resorption. However, new strategies combining antiresorptive molecules with bone anabolic drugs are likely to provide valid alternatives for skeletal health, protecting physiological bone turnover. Recently, cellular stress has been identified as a therapeutic target in both dominant and recessive forms of OI characterized by overmodified collagen I.

Skeletal abnormalities caused by a Connexin43R239Q mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or autosomal recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones. Many patients with CMD suffer from neurological symptoms. The pathogenesis of CMD is not fully understood. Treatment is limited to craniofacial surgery. Here, we report a knock in (KI) mouse model for AR CMD carrying a Cx43R239Q mutation. Cx43KI/KI mice replicate typical features of AR CMD, including thickening of craniofacial bones, club-shaped femurs, and widen

The three-dimensional structure of medullary bone: Novel criteria for the identification of avian sex-specific bone tissue.

Medullary bone is a fast-growing, ephemeral bone tissue found inside the bone cavities of female birds. Identifying this tissue in the bones of fossil avian and non-avian dinosaurs has the potential to determine which specimens represent reproductively mature females. However, difficulties in distinguishing medullary bone from superficially similar bone pathologies has led to uncertainty as to whether some specimens previously thought to contain medullary bone instead represent sick or injured individuals. The most frequently mentioned of these pathologies is avian osteopetrosis, a virally-ind

The Sirt1/FOXO signal pathway involves in regulating osteomyelitis progression via modulating mitochondrial dysfunctions and osteogenic differentiation.

The Sirtuin-1 (Sirt1) gene has been reported to be closely associated with the progression of multiple diseases, but its role in regulating osteomyelitis (OM) pathogenesis has not been explored. The murine long bone-derived osteocyte-like MLO-Y4 cells and osteoblast-like MC3T3-E1 cells were exposed to Staphylococcal protein A (SpA) treatment to establish the in vitro OM models. The expression levels of Osteoblast-specific genes (OCN, OPN and RUNX2), osteoclastic genes (CTSK, MMP9 and ACP5) and the FOXO pathway-related proteins (FOXO1, p-FOXO1, FOXO3 and p-FOXO3) were detected by performing Rea

Integrating Mechanics and Bioactivity: A Detailed Assessment of Elasticity and Viscoelasticity at Different Scales in 2D Biofunctionalized PEGDA Hydrogels for Targeted Bone Regeneration.

Methods for promoting and controlling the differentiation of human mesenchymal stem cells (hMSCs) in vitro before in vivo transplantation are crucial for the advancement of tissue engineering and regenerative medicine. In this study, we developed poly(ethylene glycol) diacrylate (PEGDA) hydrogels with tunable mechanical properties, including elasticity and viscoelasticity, coupled with bioactivity achieved through the immobilization of a mixture of RGD and a mimetic peptide of the BMP-2 protein. Despite the key relevance of hydrogel mechanical properties for cell culture, a standard for its ch

The transcription factor BBX regulates phosphate homeostasis through the modulation of FGF23.

Fibroblast growth factor 23 (FGF23) plays an important role in phosphate homeostasis, and increased FGF23 levels result in hypophosphatemia; however, the molecular mechanism underlying increased FGF23 expression has not been fully elucidated. In this study, we found that mice lacking the bobby sox homolog (Bbx-/-) presented increased FGF23 expression and low phosphate levels in the serum and skeletal abnormalities such as a low bone mineral density (BMD) and bone volume (BV), as well as short and weak bones associated with low bone formation. Osteocyte-specific deletion of Bbx using Dmp-1-Cre

Tissue changes and tissue reactivity following osteotomy by a conventional rotary device, an ultrasonic unit, and an Er: YAG laser - A comparative study in humans.

INTRODUCTION: Innovative technologies from other fields of science are constantly being introduced in medicine. Research works on animals st … within the superficial surface in all bone samples were generally minimal. In all specimens, intact osteocytes were detectable away from the area of direct action of the bone-cutting device. It was established, that the reactive facial edema, pain levels, and jaw disfunction were with milder values following in vivo osteotomy by an ultrasonic unit and Er: YA …

Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management.

Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized matrix, whereas HPP children develop rickets and osteomalacia. We report a family, father and three children, affected with growth retardation, low bone mass and recurrent fractures.

Osteoblastic Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth by Probiotic Hydroxyapatite.

OBJECTIVE: Multipotent cells derived from human exfoliated deciduous teeth (SHED) possess the ability to differentiate into various cell types, including osteoblasts. This study aims to simulate the growth induction and osteogenic differentiation of SHED cells using probiotics and their resultant biomaterials. MATERIALS AND METHODS: This experimental study proceeded in two stages. Initially, we evaluated the effect of autoclaved nutrient agar (NA) grown probiotic Bacillus coagulans (B. coagulans) on the SHED and MG-63 cell lines. Subsequently, probiotics grown on the Pikovskaya plus urea (PVK