Effects of ovariectomy on turnover of alveolar bone in the healed extraction socket in rat edentulous mandible.

Objective: The number of patients with postmenopausal osteoporosis receiving dental implants because of edentulism is increasing. Since osseointegration around implants requires formation and maintenance of new bone, knowledge of how ovariectomy (OVX) affects turnover of mandibular and maxillary bone is required. In the present study, we investigated the effects of OVX on turnover of alveolar bone in the healed extraction socket of the rat left mandibular incisor.

Fibronectin inhibits osteoclastogenesis while enhancing osteoclast activity via nitric oxide and interleukin-1β-mediated signaling pathways.

Osteoclasts are bone-resorbing cells formed by fusion of mononuclear precursors. The matrix proteins, fibronectin (FN), vitronectin (VN), and osteopontin (OPN) are implicated in joint destruction and interact with osteoclasts mainly through integrins. To assess the effects of these matrix proteins on osteoclast formation and activity, we used RAW 264.

Bone matrix proteins and extracellular acidification: potential co-regulators of osteoclast morphology.

Osteoclasts are signaled by the bone matrix proteins fibronectin (FN), vitronectin (VN), and osteopontin (OPN) via integrins. To perform their resorptive function, osteoclasts cycle between compact (polarized), spread (non-resorbing) and migratory morphologies. Here we investigate the effects of matrix proteins on osteoclast morphology and how those effects are mediated using RAW 264.

VEGF-A expression in osteoclasts is regulated by NF-kappaB induction of HIF-1alpha.

Large osteoclasts (10+ nuclei), predominant in rheumatoid arthritis and periodontal disease, have higher expression of proteases and activating receptors and also have increased resorptive activity when compared to small (2-5 nuclei) osteoclasts. We hypothesized that large and small osteoclasts activate different signaling pathways. A Signal Transduction Pathway Finder Array was used to compare gene expression of large and small osteoclasts in RAW 264.

IL-1alpha and IL-1beta have different effects on formation and activity of large osteoclasts.

Interleukin 1 (IL-1) is a proinflammatory cytokine upregulated in conditions such as rheumatoid arthritis and periodontal disease. Both isoforms, IL-1alpha and IL-1beta, have been shown to activate osteoclasts (OCs), the cells responsible for resorbing bone. Inflammatory conditions are also characterized by increased bone loss and by the presence of large OCs (10+ nuclei).

Implantable cardioverter defibrillator therapy for prevention of sudden cardiac death in children in the Netherlands.

Introduction: Implantable cardioverter defibrillator (ICD) therapy is increasingly used in children. The purpose of this multicenter study is to evaluate mid-term clinical outcome and to identify predictors for device discharge in pediatric ICD recipients.

Methods And Results: From 1995 to 2006, 45 patients in The Netherlands under the age of 18 years received an ICD.

Left ventricular ejection fraction as criterion for implantation of an implantable cardioverter-defibrillator in heart failure patients undergoing surgical left ventricular reconstruction.

Background: Besides implantation of an implantable cardioverter-defibrillator (ICD), a proportion of patients with left ventricular (LV) dysfunction due to ischemic cardiomyopathy are potential candidates for surgical LV reconstruction (Dor procedure), which changes LV ejection fraction (LVEF) considerably. In these patients, LVEF as selection criterium for ICD implantation may be difficult. This study aimed to determine the value of LVEF as criterium for ICD implantation in heart failure patients undergoing surgical LV reconstruction.

Comparison of the effect of ovariectomy on bone mass in dentate and edentulous mandibles of adult rats.

We investigated the effect of ovariectomy (OVX) on bone changes in the edentulous and dentate mandibles and compared these to changes in tibiae and femorae using dual energy x-ray absorptiometry (DEXA) and histomorphometric measurements. One hundred and fifteen female rats had their molars and the incisor on one side of the mandible extracted at six months of age and allowed to heal for 4 months. At 10 months of age, animals were divided into an experimental group, which underwent bilateral ovariectomy, and a control group of intact animals.

Short-term effect of ovariectomy on osteoprogenitors in the healing rat mandibular incisor extraction socket.

Unlabelled: OVX increased the percentage of AP-positive CFU-F in healing rat mandible. The increase of the number of osteoprogenitors was not significant in rat mandible-derived cultures but was in femur-derived ones. This suggests that the effect of OVX on osteoprogenitors is either smaller or develops later in mandible relative to femur.

Ovariectomy of 12-month-old rats: effects on osteoprogenitor numbers in bone cell populations isolated from femur and on histomorphometric parameters of bone turnover in corresponding tibia.

Ovariectomy (OVX) in rats results in increased bone turnover and decreased bone volume and bone mineral density when measured in the metaphyses of long bones. We have investigated the effects of OVX on changes in the number of progenitors in cell populations derived from the metaphyseal bone of femurs of ovariectomized rats at 12 months of age, by using colony assays, bone nodule assays, and limiting dilution analysis at 1.5 and 9 months post-OVX.

Effects of Vitaxin, a novel therapeutic in trial for metastatic bone tumors, on osteoclast functions in vitro.

The integrin alphavbeta3 mediates cell-matrix interactions. Vitaxin(R), a humanized monoclonal antibody that blocks human and rabbit alphavbeta3 integrins, is in clinical trials for metastatic melanoma and prostate cancer. alphavbeta3 is the predominant integrin on osteoclasts, the cells responsible for bone resorption in health and disease.

Increased expression of activating factors in large osteoclasts could explain their excessive activity in osteolytic diseases.

Large osteoclasts (>or=10 nuclei) predominate at sites of pathological bone resorption. We hypothesized this was related to increased resorptive activity of large osteoclasts and have demonstrated previously that larger osteoclasts are 8-fold more likely to be resorbing than small osteoclasts (2-5 nuclei). Here we ask whether these differences in resorptive activity can be explained by differences in expression of factors involved in osteoclast signaling, fusion, attachment, and matrix degradation.

Effect of age on progesterone receptor expression, and osteoprogenitor proliferation and differentiation in female rat vertebral cell populations.

In the present investigation, we evaluated whether the capacity for proliferation and differentiation of progesterone (Prog)-dependent osteoprogenitors in the female rat skeleton is related to the level of Prog receptors (PRs) and/or the level of circulating estrogen. We confirmed that in rats, estrogen levels at 18 months of age are higher than those at 3 months, and higher again in rats of 22.5, 25.

Different effects of insulin and insulin-like growth factors I and II on osteoprogenitors and adipocyte progenitors in fetal rat bone cell populations.

We investigated the effects of insulin (1-1,000 nM), insulin-like growth factor (IGF)-I, and IGF-II (3-100 nM each) alone or together with 10 nM dexamethasone (DEX) or 10 nM 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) on proliferation and differentiation of adipocyte and osteoblast progenitors in bone cell populations derived from fetal rat calvaria. The effects on differentiation were evaluated by counting the number of bone or osteoid nodules and adipocyte colonies and the effects on proliferation, by measuring their size by image analysis. The types of cells studied were 1,25(OH)(2)D(3)- and DEX-responsive adipocyte progenitors and DEX-dependent and independent osteoprogenitors.

Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity.

V-ATPases are multimeric proton pumps. The 100-kDa "a" subunit is encoded by four isoforms (a1-a4) in mammals and two (Vph1p and Stv1p) in yeast. a3 is enriched in osteoclasts and is essential for bone resorption, whereas a4 is expressed in the distal nephron and acidifies urine.

Effects of hind limb unloading and reloading on nitric oxide synthase expression and apoptosis of osteocytes and chondrocytes.

In rat bone, the absence of mechanical load results in a reduction in bone formation, inhibition of longitudinal growth, and a decrease in the number of osteoblasts and osteoprogenitors in cancellous bone. Unloading has also been linked to an increase in apoptosis of osteocytes and chondrocytes through production of nitric oxide (NO) and increased expression of NO synthases (NOS). Reloading results in recovery of bone volume within 14 days, although osteoblast and osteoclast numbers remain below control values, suggesting decreased bone turnover.

The effect of reloading on bone volume, osteoblast number, and osteoprogenitor characteristics: studies in hind limb unloaded rats.

Skeletal unloading during space flight results in bone loss. In astronauts the extent to which bone is lost varies greatly between different bones of the skeleton as well as between different individuals. Following return to earth, recovery of bone mass during reloading also varies between different bones and different individuals.

Inhibition of osteoclast differentiation by polycyclic aryl hydrocarbons is dependent on cell density and RANKL concentration.

We investigated the effect of representative polycyclic aryl hydrocarbons (PAHs), benzo[a]pyrene (BaP), and 7,12-dimethylbenz[a]anthracene (DMBA) on osteoclast differentiation and function by using dispersed cancellous bone derived rabbit osteoclasts and the RAW264.7 cells. These cells differentiate into osteoclasts when exposed to receptor activator of NF-kappaB ligand (RANKL).

Osteoprogenitor viability in cell populations isolated from rat femora is not affected by 24 h storage at 4 degrees C.

This study was initiated to determine whether partially dissected bones of rats could be refrigerated for 24 h in saline without losing viability of progenitor cells, specifically osteoprogenitors. This is directly applicable to studies involving bone tissue requiring overnight shipment, for example, studies involving space flown animals, grafting experiments, or transplantation. We evaluated cell populations isolated from the proximal femur of 6-week-old male Fisher 344 rats.

Pregnancy-associated plasma protein-A proteolytic activity in rat vertebral cell cultures: stimulation by dexamethasone--a potential mechanism for glucocorticoid regulation of osteoprogenitor proliferation and differentiation.

Glucocorticoids (GCs) at physiological concentrations stimulate osteoprogenitor proliferation and differentiation in rat bone cell populations, and this is mediated in part by an increased response to insulin-like growth factors (IGFs). Since IGF binding proteins (IGFBPs) modulate IGF actions, we evaluated whether the increased IGF responsiveness might be associated with decreased inhibitory IGFBP-4 peptide levels. Rat vertebral cells were cultured for up to 20 days with or without dexamethasone (Dex).

Effect of simulated weightlessness on osteoprogenitor cell number and proliferation in young and adult rats.

Experiments with rats flown in space or hind limb unloaded (HU) indicate that bone loss in both conditions is associated with a decrease in bone volume and osteoblast surface in cancellous and cortical bone. We hypothesize that the decrease in osteoblastic bone formation and osteoblast surface is related to a decrease in the number of osteoprogenitors and/or decreased proliferation of their progeny. We tested this hypothesis by evaluating the effect of 14 days of HU on the number of osteoprogenitors (osteoblast colony forming units; CFU-O), fibroblastic colony forming units (CFU-F), and alkaline phosphatase-positive CFU (CFU-AP) in cell populations derived from the proximal femur (unloaded) and the proximal humerus (normally loaded) in 6-week-old and 6-month-old rats.

Number, frequency, self-renewal, and expansion of osteoprogenitor cells (CFU-O) in subcultured female rat vertebral cell populations.

The present study was undertaken to determine whether the frequency and/or number of dexamethasone- and progesterone-responsive osteoprogenitors in cell populations derived from vertebrae of 6-week-old female rats could be increased relative to that of other progenitors. Frequencies and numbers of both progenitor types were determined for up to six subcultures using continuous subculturing, limiting dilution analysis, and colony assays. In dexamethasone-containing medium, subculturing resulted in an eightfold increase in the total number of dexamethasone-responsive osteoprogenitors and a 14-fold increase in progesterone-responsive osteoprogenitors in second subculture cells over first subculture cells without a significant increase in the frequency of these progenitors.

The relative contribution of cysteine proteinases and matrix metalloproteinases to the resorption process in osteoclasts derived from long bone and scapula.

It has been suggested that functional heterogeneity exists between osteoclasts from different bone sites. This could be exploited to design therapeutics that would selectively inhibit bone resorption only at compromised sites. To further investigate the existence of functional differences between osteoclasts from different bone sites we assessed whether osteoclasts isolated from intramembranous bone differ from osteoclasts isolated from endochondral bone in the extent that they utilize cysteine proteinases and matrix metalloproteinases to degrade the organic matrix of bone.

Quantitative assessment of post-extraction healing and alveolar ridge remodelling of the mandible in female rats.

Objective: To quantitatively evaluate the healing and bone changes in the mandible of adult female rats following unilateral extraction of the mandibular molars and the incisor.

Methods: Six-month old female rats had their mandibular molars and the incisor on one side of the mandible extracted. Nine rats were sacrificed at 0, 14, 28, 56 and 112 days post-extraction.

Effect of ovariectomy on dexamethasone- and progesterone-dependent osteoprogenitors in vertebral and femoral rat bone cell populations.

We have found previously that the skeleton of adult female rats contains dexamethasone (Dex)- and progesterone (Prog)-dependent osteoprogenitors, and that estrogen treatment in vitro upregulates proliferation and differentiation of the Prog-dependent but not of the Dex-dependent osteoprogenitors (Bone 1997;20:17-25). The purpose of the present study was to determine whether ovariectomy (OVX) would have different effects on these two classes of osteoprogenitors. Six-month-old Sprague-Dawley rats underwent OVX and the lumbar vertebrae and proximal femurs were collected 1.