Development and characterization of an fluorescently tagged 3D bone-cartilage interface model.

Three-dimensional cultures are widely used to study bone and cartilage. These models often focus on the interaction between osteoblasts and osteoclasts or osteoblasts and chondrocytes. A culture of osteoblasts, osteoclasts and chondrocytes would represent the cells that interact in the joint and a model with these cells could be used to study many diseases that affect the joints.

Methodology and Characterization of a 3D Bone Organoid Model Derived from Murine Cells.

Here, we report on the development of a cost-effective, well-characterized three-dimensional (3D) model of bone homeostasis derived from commonly available stocks of immortalized murine cell lines and laboratory reagents. This 3D murine-cell-derived bone organoid model (3D-mcBOM) is adaptable to a range of contexts and can be used in conjunction with surrogates of osteoblast and osteoclast function to study cellular and molecular mechanisms that affect bone homeostasis in vitro or to augment in vivo models of physiology or disease. The 3D-mcBOM was established using a pre-osteoblast murine cell line, which was seeded into a hydrogel extracellular matrix (ECM) and differentiated into functional osteoblasts (OBs).

Navigating Uncertainty: Experiences of Older Adults in Wuhan during the 76-Day COVID-19 Lockdown.

The COVID-19 pandemic continues to affect the world. Wuhan, the epicenter of the outbreak, underwent a 76-day lockdown. Research has indicated that the lockdown negatively impacted the quality of life of older individuals, but little is known about their specific experiences during the confinement period.

Effect of Vancomycin Applied to the Surgical Site on Fracture Healing in a Diabetic Rat Model.

Background: Prophylactic vancomycin treatment decreases the prevalence of surgical site and deep infections by >70% in diabetic patients undergoing reconstructive foot and ankle surgery. Thus, determining whether clinically relevant local vancomycin doses affect diabetic fracture healing is of medical interest. We hypothesized that application of vancomycin powder to the fracture site during surgery would not affect healing outcomes, but continuous exposure of vancomycin would inhibit differentiation of osteoblast precursor cells and their osteogenic activity in vitro.

Local zinc treatment enhances fracture callus properties in diabetic rats.

The effects of locally applied zinc chloride (ZnCl ) on early and late-stage parameters of fracture healing were evaluated in a diabetic rat model. Type 1 Diabetes has been shown to negatively impact mechanical parameters of bone as well as biologic markers associated with bone healing. Zinc treatments have been shown to reverse those outcomes in tests of nondiabetic and diabetic animals.

A functional three-dimensional microphysiological human model of myeloma bone disease.

Human myeloma bone disease (MBD) occurs when malignant plasma cells migrate to the bone marrow and commence inimical interactions with stromal cells, disrupting the skeletal remodeling process. The myeloma cells simultaneously suppress osteoblastic bone formation while promoting excessive osteoclastic resorption. This bone metabolism imbalance produces osteolytic lesions that cause chronic bone pain and reduce trabecular and cortical bone structural integrity, and often culminate in pathological fractures.

Local insulin application has a dose-dependent effect on lumbar fusion in a rabbit model.

The purpose of this study was to determine if locally applied insulin has a dose-responsive effect on posterolateral lumbar fusion. Adult male New Zealand White rabbits underwent posterolateral intertransverse spinal fusions (PLFs) at L5-L6 using suboptimal amounts of autograft. Fusion sites were treated with collagen sponge soaked in saline (control, n = 11), or with insulin at low (5 or 10 units, n = 13), mid (20 units, n = 11), and high (40 units, n = 11) doses.

Zinc chloride affects chondrogenesis via VEGF signaling.

Insulin mimetics, including zinc containing compounds, have previously been shown to influence chondrogenesis as it relates to healing of fractures in various preclinical models. However, the mechanism by which these compounds drive chondrogenic differentiation is yet undefined. Here, via next-generation sequencing (NGS) and in vitro functional validation, we show that Zinc Chloride (ZnCl) induces expression of both chondrogenic genes (Sox9, Runx1, collagen) as well as genes associated with VEGF-mediated signal transduction, including VEGF receptors 1 and 2 and their ligands; VEGF-A and VEGF-B.

Genetic variants as biomarkers for progression and resistance in multiple myeloma.

Technical advances in genome sequencing, in particular whole-genome sequencing (WGS), provide adequate tools to understanding cancer at the molecular level while specifically focusing on genetic variants that contribute to the causation and progression of pathogenic cancers. Multiple myeloma (MM), a malignant disease of plasma cells that is marked as rare yet incurable, may be diagnosed by WGS tools, as this cancer is associated with chromosomal translocations and mutations in specific protein-coding genes. Among these protein-coding genes, many are known to be responsible for cell cycle regulation in MM.

A meta-analysis of the effect of binge drinking on the oral microbiome and its relation to Alzheimer's disease.

The diversity of bacterial species in the oral cavity makes it a key site for research. The close proximity of the oral cavity to the brain and the blood brain barrier enhances the interest to study this site. Changes in the oral microbiome are linked to multiple systemic diseases.

CDllb+ targeted depletion of macrophages negatively affects bone fracture healing.

Inflammation is an important part of the fracture repair process which requires osteogenic cells to interact with innate immune cells such as macrophages. All murine macrophages express the F4/80 cell surface marker but they may be further subdivided into two main phenotypes: M1 (proinflammatory) or M2 (anti-inflammatory) based on surface marker expression and function. Macrophages polarize between these two main classes in response to inflammation while differentially regulating the healing process.

Bi-directional Acceleration of Alcohol Use and Opioid Use Disorder.

Alcohol is the most widely used addictive substance. Severe alcohol abuse is diagnosed as "alcohol use disorder" (AUD). A common and harmful drinking pattern is binge drinking that elevates a person's blood alcohol concentration to ≥ 0.

Zinc as a Therapeutic Agent in Bone Regeneration.

Zinc is an essential mineral that is required for normal skeletal growth and bone homeostasis. Furthermore, zinc appears to be able to promote bone regeneration. However, the cellular and molecular pathways through which zinc promotes bone growth, homeostasis, and regeneration are poorly understood.

Kinases: Understanding Their Role in HIV Infection.

Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. The drawback of these drugs is that they lack antiviral mechanisms that account for resistance or viral mutation. Thus, there is a pressing need for researchers to explore and investigate new therapeutic agents with other antiviral strategies.

Macrophage subtype and cytokine expression characterization during the acute inflammatory phase of mouse bone fracture repair.

Fracture repair is a complex process requiring heterotypic interactions between osteogenic cells and immune cells. Recent evidence indicates that macrophages are critically involved in fracture repair. Polarized macrophage populations differentially promote and regulate inflammation in other tissues, but little is known about the various macrophage subtypes and their signaling activities following a bone fracture.

Meta-analysis of alcohol induced gut dysbiosis and the resulting behavioral impact.

About 99% of the unique genes and almost half of the cells found in the human body come from microbes including bacteria, archaea, fungi, and viruses. Collectively these microorganisms contribute to the microbiome and often reside in the gut. The gut microbiome plays an important role in the body and contributes to digestive health, the immune system, and brain function.

A Meta-Analysis of Non-Osteoarthritis and Osteoarthritis Chondrocyte Gene Expression to Determine the Efficacy of Autologous Chondrocyte Transplantation as a Viable Treatment Option.

Background: Osteoarthritis (OA) is a clinical syndrome characterized by joint failure that is accompanied by pain and functional limitations. OA is the leading cause of chronic disability in elderly and it is estimated that the United States spends $185 billion in management of OA annually. Although OA patients receive both pharmacologic and non-pharmacologic treatments, none of them provide long-lasting treatments.

Bone Morphogenetic Proteins (BMPs) and Bone Regeneration.

Many research methods exist to elucidate the role of BMP-2 during bone regeneration. This chapter briefly reviews important animal models used in these studies and provides details on the rat femur defect model. This animal model is frequently utilized to measure the efficacy of osteogenic factors like BMP-2.

Common Cell Lines Used to Study Bone Morphogenetic Proteins (BMPs).

Many research methods exist to elucidate the functions of BMPs during osteogenesis. This chapter briefly reviews common immortalized mesenchymal cell types used to measure the efficacy of osteogenic factors like BMP-2. Detailed information regarding media and culture conditions are provided.

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis.

Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion.

Effects of local vanadium delivery on diabetic fracture healing.

This study evaluated the effect of local vanadyl acetylacetonate (VAC), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, and radiographic scoring were performed, as well as histomorphometry, including percent bone, percent cartilage, and osteoclast numbers. Fractures treated with local 1.

Local Zinc Chloride Release From a Calcium Sulfate Carrier Enhances Fracture Healing.

Background: This study examined the efficacy of calcium sulfate (CaSO4) as a carrier for intramedullary delivery of zinc chloride (ZnCl2) to treat fracture healing in a BB Wistar rat model. A non-carrier-mediated injection of 3.0 mg/kg of ZnCl2 has previously been shown to enhance fracture healing.

The Biology of Bone and Ligament Healing.

This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions.

Variation in lipid mediator and cytokine levels during mouse femur fracture healing.

Fracture healing is regulated by a variety of inflammatory mediators and growth factors which act over time to regenerate the injured tissue. This study used a mouse femur fracture model to quantify the temporal expression pattern of lipid mediators, cytokines, and related mRNAs during healing. Cyclooxygenase (COX-1 and COX-2) and 5-lipoxygenase (5-LO) derived lipid mediators, cytokines, and mRNA levels were quantified using mass spectrometry (LC-MS/MS), bead-based multiplex assays (xMAP), and quantitative PCR of cDNA (RTqPCR), respectively.