Enhanced Bone Remodeling After Fracture Priming.

The immune system is an active component of bone repair. Mast cells influence the recruitment of macrophages, osteoclasts and blood vessels into the repair tissue. We hypothesized that if mast cells and other immune cells are sensitized to recognize broken bone, they will mount an increased response to subsequent fractures that may be translated into enhanced healing.

3D Printed Polyurethane Scaffolds for the Repair of Bone Defects.

Critical-size bone defects are those that will not heal without intervention and can arise secondary to trauma, infection, and surgical resection of tumors. Treatment options are currently limited to filling the defect with autologous bone, of which there is not always an abundant supply, or ceramic pastes that only allow for limited osteo-inductive and -conductive capacity. In this study we investigate the repair of bone defects using a 3D printed LayFomm scaffold.

Bone extracts immunomodulate and enhance the regenerative performance of dicalcium phosphates bioceramics.

Immunomodulation strategies are believed to improve the integration and clinical performance of synthetic bone substitutes. One potential approach is the modification of biomaterial surface chemistry to mimic bone extracellular matrix (ECM). In this sense, we hypothesized that coating synthetic dicalcium phosphate (DCP) bioceramics with bone ECM proteins would modulate the host immune reactions and improve their regenerative performance.

Defective bone repair in diclofenac treated C57Bl6 mice with and without lipopolysaccharide induced systemic inflammation.

Bone repair after trauma or surgical intervention involves a tightly regulated cascade of events that starts with hemostasis and an inflammatory response, which are critical for successful healing. Nonsteroidal anti-inflammatory drugs (NSAID) are routinely prescribed for pain relief despite their potential inhibitory effect on bone repair. The goal of this study was to determine the impact of administration of the non-selective NSAID diclofenac in the inflammatory phase of bone repair in mice with or without lipopolysaccharide-induced systemic inflammation.

Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic.

Profile of bacteria colonizing the exposed bone of patients with anti-osteoclastic drug-related osteonecrosis of the jaws.

Microbial etiology for anti-osteoclastic drug-related osteonecrosis of the jaw (ARONJ) was suggested. This study investigates any link between bacteria colonizing ARONJ sites and other oral cavity sites. Microbiota samples of 10 ARONJ patients were collected from the exposed bone, adjacent teeth, contralateral teeth, and tongue.

Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model.

Osteonecrosis of the femoral head (ONFH) is a potentially devastating complication that occurs in up to 40% of young adults receiving chronic glucocorticoid (GC) therapy. Through a validated GC therapy rat model, we have previously shown that Wistar Kyoto (WK) rats exhibit a genetic susceptibility to GC-induced ONFH compared to Sasco Fischer (F344) rats. We have undertaken this study in order to investigate differences between these two strains for their bone parameters, alpha-2-macroglobulin (A2M) circulating levels and incidence of GC-induced osteonecrosis of the femoral head.

Characterization of a Pre-Clinical Mini-Pig Model of Scaphoid Non-Union.

A fractured scaphoid is a common disabling injury that is frequently complicated by non-union. The treatment of non-union remains challenging because of the scaphoid's small size and delicate blood supply. Large animal models are the most reliable method to evaluate the efficacy of new treatment modalities before their translation into clinical practice.

High density infill in cracks and protrusions from the articular calcified cartilage in osteoarthritis in standardbred horse carpal bones.

We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC).

Micro CT Analysis of Spine Architecture in a Mouse Model of Scoliosis.

Objective: Mice homozygous for targeted deletion of the gene encoding fibroblast growth factor receptor 3 (FGFR3(-/-)) develop kyphoscoliosis by 2 months of age. The first objective of this study was to use high resolution X-ray to characterize curve progression in vivo and micro CT to quantify spine architecture ex vivo in FGFR3(-/-) mice. The second objective was to determine if slow release of the bone anabolic peptide parathyroid hormone related protein (PTHrP-1-34) from a pellet placed adjacent to the thoracic spine could inhibit progressive kyphoscoliosis.

A novel role for interferon regulatory factor 1 (IRF1) in regulation of bone metabolism.

Increased risk of bone fractures is observed in patients with chronic inflammatory conditions, such as inflammatory bowel disease and rheumatoid arthritis. Members of the Interferon Response Factor family of transcriptional regulators, IRF1 and IRF8, have been identified as genetic risk factors for several chronic inflammatory and autoimmune diseases. We have investigated a potential role for the Irf1 gene in bone metabolism.

Bisphosphonates inhibit bone remodeling in the jaw bones of rats and delay healing following tooth extractions.

Objective: This study aimed to evaluate the impact of concurrent administration of clinically relevant doses of zoledronic acid (ZA) and dexamethasone (DX) on bone healing after tooth extraction (EXO).

Materials And Methods: Forty-four Sprague-Dawley rats (6-8 month old) were randomized into five groups: ZA + DX = weekly injection of ZA with DX for 7 weeks; WD = ZA with DX for 3 weeks then DX alone for 4 weeks; C = control saline for 7 weeks; ZA = ZA alone for 7 weeks and DX = DX alone for 7 weeks. ZA was administered at 0.

Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice.

Matrix gla protein (MGP), a potent inhibitor of extracellular matrix (ECM) mineralization, is primarily produced by vascular smooth muscle cells (VSMCs) and chondrocytes. Consistent with its expression profile, MGP deficiency in mice (Mgp-/- mice) results in extensive mineralization of all arteries and cartilaginous ECMs. Interestingly, we observed a progressive loss of body weight in Mgp-/- mice, which becomes apparent by the third week of age.

The G60S connexin 43 mutation activates the osteoblast lineage and results in a resorption-stimulating bone matrix and abrogation of old-age-related bone loss.

We previously isolated a low bone mass mouse, Gja1(Jrt) / + , with a mutation in the gap junction protein, alpha 1 gene (Gja1), encoding for a dominant negative G60S Connexin 43 (Cx43) mutant protein. Similar to other Cx43 mutant mouse models described, including a global Cx43 deletion, four skeletal cell conditional-deletion mutants, and a Cx43 missense mutant (G138R/ +), a reduction in Cx43 gap junction formation and/or function resulted in mice with early onset osteopenia. In contrast to other Cx43 mutants, however, we found that Gja1(Jrt) /+ mice have both higher bone marrow stromal osteoprogenitor numbers and increased appendicular skeleton osteoblast activity, leading to cell autonomous upregulation of both matrix bone sialoprotein (BSP) and membrane-bound receptor activator of nuclear factor-κB ligand (mbRANKL).

Assessing the oral microbiota of healthy and alcohol-treated rats using whole-genome DNA probes from human bacteria.

Objective: This study aimed to evaluate the capacity of whole-genome DNA probes prepared from human oral bacteria to cross-react with bacteria from the oral cavity of rats, and to assess the influence of alcohol ingestion on the animals' oral biofilm.

Design: Twenty four mature Wistar rats were equally divided in two groups. One group (control) was fed balanced diet of rat pellets and water.

Mesenchymal stem cell transplantation to promote bone healing.

An overall decline in the availability of osteogenic precursor cells and growth factors in the bone marrow microenvironment have been associated with impaired bone formation and osteopenia in humans. The objective of the current study was to determine if transplantation of mesenchymal stromal cells (MSC) from a healthy, young donor mouse into an osteopenic recipient mouse could enhance osseointegration of a femoral implant. MSC harvested from normal young adult mice differentiated into bone forming osteoblasts when cultured on implant grade titanium surfaces ex vivo and promoted bone formation around titanium-coated rods implanted in the femoral canal of osteopenic recipient mice.

T cell protein tyrosine phosphatase deficiency results in spontaneous synovitis and subchondral bone resorption in mice.

Objective: T cell protein tyrosine phosphatase (TC-PTP) is an important regulator of hematopoiesis and cytokine signaling. Recently, several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) in the locus of TC-PTP that are associated with rheumatoid arthritis and juvenile idiopathic arthritis, among other autoimmune diseases. The aim of this study was to evaluate the effect of TC-PTP deficiency on the bone and joint environment using a knockout mouse model.

Response of murine bone marrow-derived mesenchymal stromal cells to dry-etched porous silicon scaffolds.

Porous silicon shows great promise as a bio-interface material due to its large surface to volume ratio, its stability in aqueous solutions and to the ability to precisely regulate its pore characteristics. In the current study, porous silicon scaffolds were fabricated from single crystalline silicon wafers by a novel xenon difluoride dry etching technique. This simplified dry etch fabrication process allows selective formation of porous silicon using a standard photoresist as mask material and eliminates the post-formation drying step typically required for the wet etching techniques, thereby reducing the risk of damaging the newly formed porous silicon.

The V-ATPase a3 subunit mutation R740S is dominant negative and results in osteopetrosis in mice.

A mouse founder with high bone mineral density and an osteopetrotic phenotype was identified in an N-ethyl-N-nitrosourea (ENU) screen. It was found to carry a dominant missense mutation in the Tcirg1 gene that encodes the a3 subunit of the vacuolar type H(+)-ATPase (V-ATPase), resulting in replacement of a highly conserved amino acid (R740S). The +/R740S mice have normal appearance, size, and weight but exhibit high bone density.

Reduced hydraulic permeability of three-dimensional collagen scaffolds attenuates gel contraction and promotes the growth and differentiation of mesenchymal stem cells.

Optimal scaffold characteristics are essential for the therapeutic application of engineered tissues. Hydraulic permeability (k) affects many properties of collagen gels, such as mechanical properties, cell-scaffold interactions within three dimensions (3D), oxygen flow and nutrient diffusion. However, the cellular response to 3D gel scaffolds of defined k values has not been investigated.

FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line.

The signaling axis comprising the parathyroid hormone (PTH)-related peptide (PTHrP), the PTH/PTHrP receptor and the fibroblast growth factor receptor 3 (FGFR3) plays a central role in chondrocyte proliferation. The Indian hedgehog (IHH) gene is normally expressed in early hypertrophic chondrocytes, and its negative feedback loop was shown to regulate PTH/PTHrP receptor signaling. In this study, we examined the regulation of PTH/PTHrP receptor gene expression in a FGFR3-transfected chondrocytic cell line, CFK2.

Nanotechnology and bone healing.

Nanotechnology and its attendant techniques have yet to make a significant impact on the science of bone healing. However, the potential benefits are immediately obvious with the result that hundreds of researchers and firms are performing the basic research needed to mature this nascent, yet soon to be fruitful niche. Together with genomics and proteomics, and combined with tissue engineering, this is the new face of orthopaedic technology.

Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown.

Age-related bone loss in the LOU/c rat model of healthy ageing.

Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time.

Persistent osteopenia in adult cystic fibrosis transmembrane conductance regulator-deficient mice.

Rationale: A loss of function mutation in the cystic fibrosis transmembrane conductance regulator gene is believed to be an independent risk factor for bone disease in patients with cystic fibrosis.

Objectives: The objective of this work was to use congenic mice as a preclinical model to examine the bone phenotype of Cftr(-/-) mice and control littermates at 8, 12, and 28 weeks of age.

Methods: The bone phenotype of control and Cftr(-/-) mice was evaluated by quantitative imaging, histologic and histomorphometric analyses, and serum levels of bone biomarkers.