Design of artificial metalloenzymes for the reduction of nicotinamide cofactors.

Artificial metalloenzymes result from the insertion of a catalytically active metal complex into a biological scaffold, generally a protein devoid of other catalytic functionalities. As such, their design requires efforts to engineer substrate binding, in addition to accommodating the artificial catalyst. Here we constructed and characterised artificial metalloenzymes using alcohol dehydrogenase as starting point, an enzyme which has both a cofactor and a substrate binding pocket.

An unusual case of cervical lipoblastoma with review of literature.

Lipoblastoma is a rare, benign, soft tissue neoplasm most commonly seen in children less than 3 years. It is usually seen on the trunk and on the limbs and rarely in the head and neck. In our case, a child of age 1 year and 3 months presented with a swelling over the nape of the neck.

Diversity of bone matrix adhesion proteins modulates osteoblast attachment and organization of actin cytoskeleton.

Interaction of cells with extracellular matrix is an essential event for differentiation, proliferation and activity of osteoblasts. In bone, binding of osteoblasts to bone matrix is required to determine specific activities of the cells and to synthesize matrix bone proteins. Integrins are the major cell receptors involved in the cell linkage to matrix proteins such as fibronectin, type I collagen and vitronectin, via the RGD-sequences.

Thiazolidinediones cause compaction of nuclear heterochromatin in the pluripotent mesenchymal cell line C3H10T1/2 when inducing an adipogenic phenotype.

Objective: To characterize the nuclear changes induced in vitro by thiazolidinediones (TZDs) in a murine pluripotent mesenchymal cell line.

Study Design: The C3H10T1/2 cell line, which can differentiate either in osteoblast or in adipocyte, was cultured in the presence of pioglitazone (5 microM) or rosiglitazone (0.5 microM) for 6, 8 and 9 days (D).

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice.

A role for the gastro-intestinal tract in controlling bone remodeling is suspected since serum levels of bone remodeling markers are affected rapidly after a meal. Glucose-dependent insulinotropic polypeptide (GIP) represents a suitable candidate in mediating this effect. The aim of the present study was to investigate the effect of total inhibition of GIP signaling on trabecular bone volume, microarchitecture and quality.

Water absorption of poly(methyl methacrylate) measured by vertical interference microscopy.

PMMA (poly(methyl methacrylate)) is widely used to prepare orthopedic cements. They are in direct contact with cells and body fluids. PMMA, despite its hydrophobic nature, can absorb ~2% w/w water.

Depth and volume of resorption induced by osteoclasts generated in the presence of RANKL, TNF-alpha/IL-1 or LIGHT.

Rheumatoid arthritis (RA) is associated with pathological bone destruction mediated by osteoclasts. Although RANKL has been reported as a crucial factor for osteoclastogenesis, several other factors increased in RA support osteoclast formation and resorption in the absence of RANKL such as TNF-alpha and LIGHT. To date, in vitro bone resorption experiments are reported as the mean area of bone resorption per cortical or dentine slices and do not provide any information about depth and volume of resorption.

Cellular and molecular effects of thiazolidinediones on bone cells: a review.

Thiazolidinediones represent a class of molecules used in the treatment of type 2 diabetes mellitus. Despite interesting effects in lowering blood glucose and HbA1c levels durably, an augmentation of the fracture risk in women has emerged in the past years. This review is providing the readers with information about the cellular and molecular mechanisms involved in bone and bone cells in response to these drugs.

Relationships between bone mass and micro-architecture at the mandible and iliac bone in edentulous subjects: a dual X-ray absorptiometry, computerised tomography and microcomputed tomography study.

Objectives: To compare bone volume, bone mineral density, cortical thickness and bone micro-architecture in a series of paired mandibular and iliac bone samples analysed by various imagery techniques to see whether relationships exist between the various techniques and between mandibular and iliac bone.

Materials And Methods: Bone samples from the mandible and ilium were harvested in 20 cadavers and analysed by dual energy X-ray absorptiometry (DXA), computerised tomography (CT) on a conventional hospital machine and microCT.

Results: Significant correlations were found between Hounsfield density obtained by CT, and bone mass determined by microCT but not with DXA values.

Does milling one-piece titanium dental implants induce osteocyte and osteoclast changes?

One-piece dental implants avoid adverse effects sometimes associated with the traditional implant-abutment interface and may provide a suitable alternative to two-piece implants; however, one-piece implants often need in situ milling, which may exacerbate cell apoptosis from excessive heat at the bone-implant interface and induce secondary crestal bone loss. Twelve implants were placed in the metaphyses of two sheep under general anesthesia. Six implants were milled with a diamond bur while the other six implants remained intact.

Bone metastasis: histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review.

The development of a bone metastasis involves interactions between the tumor cells, the bone marrow microenvironment and the bone cells themselves. A better understanding of the pathophysiological changes occurring in bone metastasis can be obtained from histopathological examination of invaded specimens. This review focuses on the main molecular mechanisms implied in the localization and growth of malignant cells in the bone marrow.

Three-dimensional characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (MicroCT).

Background: Angiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography). They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities.

New laboratory tools in the assessment of bone quality.

Bone quality is a complex set of intricated and interdependent factors that influence bone strength. A number of methods have emerged to measure bone quality, taking into account the organic or the mineral phase of the bone matrix, in the laboratory. Bone quality is a complex set of different factors that are interdependent.

Measurement by vertical scanning profilometry of resorption volume and lacunae depth caused by osteoclasts on dentine slices.

The resorption pit assay is classically used to evaluate osteoclast activity on bone or dentine slices that can be eroded by these cells. Two different types of cells were generated from peripheral blood mononuclear cells cultured in the presence of M-CSF + sRANKL or with M-CSF + LPS. At the end of the culture period (21 days), cells were discarded and the dentine slices stained with toluidine blue and examined with an NT9100 Wyco vertical scanning profilometer.

In vitro assessment of osteoblast and macrophage mobility in presence of β-TCP particles by videomicroscopy.

β-TCP is widely used to repair bone defects due to its good biocompatibility, macroporosity (favoring bone ingrowth) and bioresorbability. However, cell interactions with the biomaterial at the first times of implantation remain largely unknown. We have observed cell behaviors in direct contact with β-TCP particles using long-term culture under videomicroscopy.

Computed microtomography of bone specimens for rapid analysis of bone changes associated with malignancy.

Breast and prostate cancers are specially metastasizing to bone. Metastases from breast cancer usually exhibit a mixed osteolytic/osteosclerotic aspect, with osteolysis predominating. Osteosclerosis is a common finding in prostatic cancer although osteolysis occurs within the sclerotic lesions.

In vitro calcification of chemically functionalized carbon nanotubes.

Bone is composed of two phases. The organic phase is made of collagen fibrils assembled in broad fibers acting as a template for mineralization. The mineral phase comprises hydroxyapatite (HAP) crystals grown between and inside the collagen fibers.

A non-steroidal anti-inflammatory drug (ketoprofen) does not delay beta-TCP bone graft healing.

Beta-tricalcium phosphate (beta-TCP) is a suitable biomaterial in oral and maxillofacial surgery since it can induce a rapid proliferation of woven bone. Granules, prepared by the polyurethane foam method, were implanted in critical size defects performed in the femoral condyles of New Zealand rabbits. Animals were studied after 8 and 28 days.

Sinus lift augmentation and beta-TCP: a microCT and histologic analysis on human bone biopsies.

Sinus lift elevation is an interesting method to restore bone mass at the maxilla in edentulated patients. We have investigated the histological effects of beta tricalcium phosphate (beta-TCP) combined with autograft bone for sinus lift elevation. A series of 14 patients who were candidate for dental implantation were grafted with beta-TCP granules and morcellized autograft bone harvested at the chin.

The cathepsin K inhibitor AAE581 induces morphological changes in osteoclasts of treated patients.

Inhibitors of Cathepsin K (Cat-K) are recognized as an interesting way to inhibit osteoclast (OC) activity. OCs from patients treated with the anticathepsin-K inhibitor AAE581 (balicatib) were found enlarged. They contained numerous vacuoles filled with tartrate resistant acid phosphatase (TRAcP), an intracellular enzyme that terminates the degradation of collagen internalized in OC transcytotic vesicles.

A single pretreatment by zoledronic acid converts metastases from osteolytic to osteoblastic in the rat.

Bone metastases are severe complications of cancers associated with increased morbidity, pain, risk fracture, and reduced life span for patients. Bisphosphonates emerged as a relief treatment in bone metastases. A single dose of zoledronic acid (78 microg/kg) was injected into six Copenhagen rats 4 days before receiving an intraosseous inoculation of metastatic anaplastic tumor of lymph node and lung cell (MLL) prostate cancer cells.

Cobalt, chromium and nickel affect hydroxyapatite crystal growth in vitro.

Metals are widely used in orthopaedics and recent studies have reported that patients with metal implants have a significant increase of metal levels in serum and synovial fluid. Femoral neck fracture occurred in some patients with metal-on-metal implants for unknown reasons. Recently, bone quality has emerged as an important factor of bone strength and few studies have investigated the effects of metal ions on hydroxyapatite properties.