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Superoxide generation in transformed B-lymphocytes from patients with severe, malignant osteopetrosis.

Severe, malignant osteopetrosis is a disease characterized by osteoclasts that fail to resorb bone. Serious defects in the ability of white blood cells to eradicate infectious agents confound the clinical course. Defective superoxide generation by neutrophils, monocytes, and lymphocytes contributes to this inability to fight infection. To elucidate the mechanisms resulting in the defective superoxide generation observed in osteopetrotic leukocytes, gene expression, translocation, and phosphorylation of the major components that form the functional NADPH oxidase complex were studied in transfor…

Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis.

Osteocalcin is an abundant, highly conserved bone-specific protein that is synthesized by osteoblasts. Temporally, osteocalcin appears in embryonic bone at the time of mineral deposition, where it binds to hydroxyapatite in a calcium-dependent manner. A role for osteocalcin in bone resorption has been suggested because of its ability to influence recruitment and differentiation of osteoclasts at the bone surface. The human osteocalcin gene has been mapped to 1q25-1q31 by somatic cell hybridization. In this paper, we refine both the genetic map and the physical map of osteocalcin and describe a…

Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.

Glucocorticoid-induced bone disease is characterized by decreased bone formation and in situ death of isolated segments of bone (osteonecros … ptosis was documented in patients with glucocorticoid-induced osteoporosis. Decreased production of osteoclasts explains the reduction in bone turnover, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width. Furthermore, accumulation of apoptotic osteocytes may contribute to osteonecrosi …

Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant.

Osteopetrosis is an inherited disorder characterized by bone sclerosis due to reduced bone resorption. Here we report that human osteopetrot … ulation. Because osteoblasts were still of recipient origin post-BMT, this suggests that functional osteoclasts, due to the replacement of hematopoeitic cells, provided a local microenvironment in vivo triggering the differentiation and/or recruitment of a limited number of functional osteoblasts.

[Effect of insulin therapy on abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetic rat].

By use of histomorphometry and photon and physical, calcium homeostasis, bone morphology, bone mass and bone growth were studied in freely f … esults in reduction of bone formation and insufficient bone calcification and relative increment of osteoclasts activity. Thus, bone resorption overweight bone formation leading to a negative balance of bone remodeling. The effect of PTH and CT on bone changes in diabetic rats can't be affirmed in our experiments. It is probable that metabolic disorder and/or …

The incisor absent rat: an animal model for the study of otosclerosis.

The incisor absent (ia) rat is introduced as an animal model for the study of otosclerosis. Previous animal models have failed to accurately … cally similar to otospongiosis. The bony pathology in the incisor absent rat is caused by defective osteoclasts and transplantation of bone marrow cells from normal rats to the incisor absent rats corrects the cellular abnormality. The incisor absent rat may represent the best animal model to date for the study of otosclerosis, its cause, and clinical treatme …

Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis.

Review of the radiographs of 34 patients with autosomal dominant osteopetrosis revealed two distinct phenotypical types. Both were strictly … esting differences between the two types in bone mineral metabolism and structural functions of the osteoclasts. The two types may represent two different entities with the same mode of inheritance, and in both cases with affected bone resorption.

Prostaglandins change cell shape and increase intercellular gap junctions in osteoblasts cultured from rat fetal calvaria.

Mounting experimental evidence indicates that osteoblasts may be cellular intermediaries in the local activation of bone remodeling. To eluc … ion, shape changes in surface osteoblasts serving to expose bone surfaces which are chemotactic for osteoclasts and gap junctions propagating locally initiated activation messages.

Parathyroidectomy in chronic renal failure.

In order to establish whether parathyroidectomy altered the natural history of ectopic calcification in patients with renal failure we under … in two patients. Both had positive aluminium stains for excess aluminium in their bone. Numbers of osteoclasts and the amount of marrow fibrosis declined in parallel following parathyroidectomy, but woven bone persisted for months or years.

Estrogen and bone. Marshall R. Urist's contributions.

Estrogens have profound effects on the maintenance of bone mass. Urist's early studies showed species differences in reactions of bone to estrogens and in their ability to inhibit endosteal resorption and to reduce the number of osteoclasts. It is now clear that estrogens are anticatabolic as quantified by kinetic and radiographic studies. The clinical use of this important action of estrogens for the prevention and treatment of osteoporosis has recently been accepted by the NIH Consensus on Treatment of Osteoporosis and by the Food and Drug Administration. The relation of hip fractures to ost…

Bone changes in hypercalcemia of malignancy in dogs.

Bone was collected for trabecular bone morphometry from 6 dogs with hypercalcemia of malignancy. Five of the dogs had lymphosarcoma and 1 had an anal sac apocrine gland carcinoma with vertebral metastases. Parathyroid gland weights varied around normal, with those for 1 dog being slightly low and those for another dog being moderately increased. As a group, the dogs had decreased bone volume, with increased resorption surfaces and increased numbers of osteoclasts. In 4 dogs, osteoid seams and osteoblasts were limited in extent and this distinguished them from dogs with hyperparathyroidism. Alt…

The role of CD8+ T cells in the immunoregulation of osteoporosis.

INTRODUCTION: Osteoporosis weakens the skeleton by lowering bone mass and damaging bone microarchitecture. A growing body of evidence points to disruptions in osteoimmune homeostasis as a key driver of this disease. In particular, apoptosis of bone cells and immune cells appears to be a critical contributing mechanism. Within the bone marrow, CD8+ T cells display a surprising functional duality: whether they protect bone or promote its loss depends heavily on local signals. Under healthy conditions or after mechanical loading, activated CD8+ T cells help maintain bone mass. They do so mainly b

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… Activation of ERK signaling directly stimulates the differentiation of osteoclast precursors into mature osteoclasts and enhances the bone-resorbing activity of existing osteoclasts ( 31 ). … Upon binding to the CCR3 receptor on osteoclast precursors, CCL5 activates the ERK pathway and thereby promotes both the differentiation and the resorptive activity of mature osteoclasts ( 28 ). …

Prolonged production cycles in commercial laying hens and its bone repercussions.

This study aimed to evaluate the impact of prolonged production cycles on bone quality in Dekalb White laying hens, focusing on bone mineral … al porosity, trabecular bone resorption, Haversian canal enlargement, and a higher number of active osteoclasts. No significant correlations were observed between BMD values and serum biochemical parameters (Pearson’s and Spearman’s correlations; P > 0.05). These findings indicate that extended laying cycles combined with cage confinement negatively impact sk …

Spatial transcriptomic mapping of canine osteosarcoma reveals immune microenvironment features linked to survival.

Osteosarcoma (OSA) is the most common malignant bone tumor in dogs and serves as a translational model for human pediatric OSA due to shared … ong-term survivors. Deconvolution uncovered co-localization of immune cells such as mast cells with osteoclasts, and T/NK cells with regulatory dendritic cells. This study maps the spatial transcriptomic landscape of cOSA, highlighting immune microenvironment features and spatial gene expression patterns associated with survival. These findings provide insigh …

Effect of inactivation of the USP19 deubiquitinase gene in mice on important phenotypes of aging.

Aging is associated with many chronic conditions that increase morbidity and mortality. These include obesity, diabetes, sarcopenia, osteopo … WT cells and the KO marrow cells showed enhanced differentiation into TRAP-positive multinucleated osteoclasts. These findings identify important potential benefits as well as risks of therapeutic targeting of USP19 for the prevention or treatment of key aging related disorders.

Periodontitis induces skeletal muscle atrophy by increasing circulating levels of activin A.

Periodontitis is linked to various systemic conditions, but its impact on skeletal muscle remains unclear. Here, we utilized a ligature-indu … ses, as well as in myeloid cells infiltrating inflamed periodontal tissues and myeloid cell-derived osteoclasts. A similar upregulation pattern of INHBA was also confirmed in periodontitis-affected human tissues by scRNA-seq analysis. Furthermore, we demonstrated that serum activin A levels are increased in periodontitis-affected mice and patients. Gingival o …

FSH Signaling in Osteoporosis and Alzheimer's Disease.

PURPOSE OF REVIEW: The female sex is itself a major risk factor for both osteoporosis and Alzheimer’s disease (AD), two age–related, chronic … s, even after adjustment for estrogen. Pre–clinical studies demonstrate that FSH directly activates osteoclasts to promote bone resorption and suppresses osteoblastogenesis. Findings in Alzheimer’s disease mouse models likewise reveal that FSH binds to neuronal FSH receptors in AD–prone brain regions and accelerates amyloid and tau pathology. Population studi …

Epithelioid Osteoblastoma: Clinicopathologic Features of a Classic Case with Aggressive Behavior.

INTRODUCTION: Epithelioid osteoblastoma is a rare variant of osteoblastoma, characterized by large osteoblasts with epithelioid morphology. … n. Histology showed epithelioid osteoblast proliferation within a highly vascular stroma, scattered osteoclasts, and hemorrhagic areas, with a low Ki-67 index (< 5%) and no atypical mitoses or infiltrative growth. DIFFERENTIAL DIAGNOSIS: Osteoid osteoma, cementoblastoma, fibro-osseous lesions, and osteosarcoma were considered. Osteosarcoma was excluded due t …

Molecular networking derived from untargeted LC-MS/MS analysis to discover inhibitors of RANKL-induced osteoclastogenesis from Egyptian marine sponge-associated fungi.

In continuous search for RANKL induced osteoclastogenesis inhibitors, twenty-six fungal isolates were obtained from ten Red Sea marine spong … ere biologically evaluated. Only 1 and 8 inhibited RANKL-induced formation of mature multinucleated osteoclasts with IC50 57.14 and 38.35 µM, respectively, without cytotoxicity against RAW264 macrophages. The ADMET properties for 1 and 8 were predicated using SwissADME and pkCMS platforms. 8 showed superior solubility and lower toxicity than compound 1.

Treatment of osteopetrosis combined with fracture around femoral internal fixation: a case report.

Osteopetrosis is a rare disease caused by bone resorption disorders due to a decrease in osteoclasts or functional abnormalities, which can easily lead to secondary fractures. Currently, there are few reports on the treatment of fractures around internal fixation in such patients. Here, we report on the treatment experience of a rare case of a patient with osteopetrosis who suffered a fracture around the internal fixation of the right femur. A 59-year-old female patient suffered a right femoral intertrochanteric fracture in 2014 and was diagnosed with osteopetrosis. She underwent right femoral…