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At least 19 recordsLinked to original sources
PubMed1979

Comparison of the effects of 1,25-dihydroxycholecalciferol, prostaglandin E2, and osteoclast-activating factor with parathyroid hormone on the ultrastructure of osteoclasts in cultured long bones of fetal rats.

The effects of 1,25-dihydroxy vitamin D3 [1,25(OH)2D3], prostaglandin (PGE2), and osteoclast-activating factor (OAF) on the size of osteoclasts, nuclei, ruffled borders, and clear zones in cultured long bones of fetal rats were quantitated. In addition, the number of osteoclasts in the bones was counted and the release of calcium from the bone into the culture medium was determined. These data were compared with the corresponding effects of parathyroid hormone (PTH). All agents tested increased the size of the ruffled borders significantly after 3 h, the size of the clear zones after 12 h, and the size of the cells after 12-24 h. No important differences in sizes were noticed between the agents tested or between the agents and PTH. The number of osteoclasts was increased after 24 h of treatment with PTH, but not after the other agents. Calcium release was significantly increased for all agents between 12 and 24 h. It is concluded that bone resorption by 1,25(OH)2D3, OAF, and PGE2 is mediated primarily by increased activity of existing osteoclasts similar to PTH activation.

Animals↗
PubMed1977

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) effects on incorporation and accumulation of osteoclast nuclei.

Male rats weighing 100 g were injected with vehicle (control group), 0.4 or 4.0 mg/kg/day of ethane-1-hydroxy-1,1-diphosphonate (EHDP). Beginning after 6 days of EHDP treatment all rats received six subcutaneous injections of 3H-thymidine at 8 h intervals. The multiple labeling index of autoradiographically defined labeled cells was determined for the osteoprogenitor cells of the primary spongiosa of the proximal tibial metaphysis. The osteoclasts in the proximal tibial metaphisis were assayed for population parameters and incorporation of labeled nuclei at sequential intervals after the administration of 3H-thymidine. After 6 days of EHDP pre-treatment the multiple labeling index of the osteoprogenitor cells was reduced with 4.0 mg/kg/day dose of EHDP. At the beginning of the experimental kinetic sampling period, after the 6 days of EHDP pre-treatment, EHDP treatment resulted in significant increases in the numbers of osteoclasts, nuclei per osteoclast profile, and total osteoclast nuclei. During the sampling period, the 4.0 mg/kg/day dose of EHDP caused further increases in the number of total osteoclasts. EHDP treatment caused a marked increase in the rate of incorporation and accumulation of 3H-thymidine-labeled nuclei in osteoclasts. Thus, EHDP causes an accelerated rate of osteoclast production from percursor cells in spite of its ability to slow bone resorption. Although the origin of osteoclast nuclei is not clear, the kinetic data from this study suggests that osteoclast nuclei are not arising from osteoprogenitor cells or osteocytes in the EHDP-treated animals.

Animals↗
PubMed1977

[Paget's disease of bone: ultrastructure and cytogenesis of osteoclasts (author's transl)].

The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification. Paget osteoclasts are characterized by their high content of nuclei. Several nuclei may show paracrystalline inclusions pointing to a possible virus infection of these cells. Giant osteoclasts have an increased mobility and a high resorptive activity, manifest by the dissection of bone fragments from endosteal bone surfaces. Cell membrane interdigitations between mononuclear cells and osteoclasts occur as a morphologic concomitant of cell fusion. Frequent occurence of such cell membrane contacts seem to indicate an increased tendency to cell fusion among the mononuclear precursors of Paget-osteoclasts. Precursor cells are located in the pericapillary region, and morphologically resemble pericytes. The assumption of an increased rate of cell fusion amoungst the precursor cells of osteoclasts might explain the development of giant osteoclasts in this disease. Further studies of the paracrystalline nuclear inclusions of Paget-osteoclasts are necessary to determine whether this process can be considered to be a cytopathogenic effect of virus infection.

Aged↗
PubMedDate not supplied

The origin of the osteoclast.

The origin of the osteoclast has long been controversial. Various approaches such as traditional light microscopy, electron microscopy, microcinephotography, autoradiography, parabiosis, quail-chick nuclear marker, etc, have been used in attempts to resolve the problem. There are 2 major concepts: the view of skeletal (local) origin vs, that of extraskeletal origin (from blood-borne cells), and recently the latter view appears to have prevailed. Electron micrographic studies revealed that osteocytes and preosteoblasts can merge with pre-existing osteoclasts. Several studies by autoradiography and by quail-chick nuclear marker strongly supported the concept of extraskeletal origin. Although an alternative interpretation of the experimental results of Crelin and Koch supports the concept of skeletal origin, the majority of various experimental results by other authors would be in accordance with the following supposition: the osteoclast originates from a hematopoietic cell line (mononuclear phagocyte system) of the bone marrow which is essentially of extrinsic origin, but in the process of increasing the number of nuclei of the osteoclast, osteoblastic cells as well as osteoclastic cells can merge with the preosteoclasts or osteoclast. However, several problems regarding the origin of the osteoclast including the relation between the osteoclast and other giant cells, still remain unsolved.

Animals↗
PubMed1979

Morphology of osteoclasts in resorbing fetal rat bone explants: effects of PTH and AIF in vitro.

Osteoclastic bone resorption was studied using 45Ca-labeled fetal rat bones cultured in the presence of parathyroid hormone (PTH) and an anti-invasion factor (AIF) derived from bovine hyaline cartilage which is enriched in a collagenase inhibitor. The specific morphological expressions of osteoclasts cultured in PTH and AIF were observed in both light and electron microscopy and analyzed cytometrically. Stimulation of bone resorption with PTH revealed significant increases in the numbers and activity of osteoclasts, whereas bones cultured in the presence of AIF showed significant decreases in numbers of osteoclasts and altered cell features including the loss of osteoclast contact with bone surfaces. These structural modifications were evaluated with 45Ca release data derived from matched-pair explants of fetal rat bones, revealing the existence of a relationship between resorptive states of the cultured bones and morphological expressions of osteoclastic activity.

Animals↗
PubMed1977

[Action of calcitonin on osteoclasts in Paget's bone disease during long term treatment (author's transl)].

Comparison of biopsies from patients with Paget's bone disease before and during long-term treatment with calcitonin reveals that the ration of bone-adherent osteoclasts to free osteoclasts is not modified by the hormone. Nor does treatment alter the average number of nuclei in osteoclasts. Under electron microscopy, all the cytological anomalies of osteoclasts in Paget's bone disease and, in particular, the characteristic nuclear inclusions, persist through treatment. Thus, although such osteoclasts do react to calcitonin as demonstrated by several authors, the specific morphological anomalies remain unaffected by the treatment. It is likely that the osteoclast in Paget's bone disease is an abnormal cell with peculiarities which may be related to the yet unknown etiology of the disease.

Bone and Bones↗
PubMed1979

Enzyme histochemical characteristics of human and kitten odontoclasts and kitten osteoclasts: a comparative study using whole cells.

Methods for the histochemical demonstration of enzymes in whole cell preparations of odontoclasts and osteoclasts are described. Enzyme histochemical characteristics of human and kitten odontoclasts from resorbing primary teeth and of osteoclasts from kitten femur metaphyses were determined and compared. The enzyme profiles, times for the appearance of detectable reaction product, intensity of the reactions and localization of the reaction products were similar in all three types of giant cell. These findings suggest that odontoclasts have enzyme properties and metabolic functions similar to those of osteoclasts. Species differences appear to be minor, although the NADP-dependent enzymes are less active in human than in kitten odontoclasts. Both odontoclasts and osteoclasts are rich in enzymes concerned with energy production and possess considerable activity of enzymes usually associated with catabolic functions. Metabolic pathways are well developed in respect of the utilization of succinic, malic, glutamic, lactic and isocitric acids, beta-hydroxybutyric acid and glucose-6-phosphate, and they also possess phosphatases, non-specific esterases and leucine naphthylamidase. The distribution of enzyme reaction products for the individual enzymes demonstrated is consistent with the presence in these cells of large numbers of mitochondria and lysosome-like organelles. Considerable phosphatase activity is demonstrable in both odontoclasts and osteoclasts at both neutral and acid pH.

Animals↗
PubMed1979

Low-calcium/high-phosphorus rickets in rats. II. Osteoclast changes.

Weanling rats were given a low Ca (0.003%)/high P (0.64%) diet with and without vitamin D for periods up to 6 weeks. An ultrastructural examination of selected areas of the proximal tibial metaphysis was carried out to study osteoclasts and their relation to calcified and uncalcified bone tissue. Osteoclasts were seen with ruffled borders adjacent to unmineralized osteoid or with their processes penetrating small patches of calcified osteoid tissue. In both cases the calcified bone margin had a 'frayed edge', suggesting that osteoclasts are capable of chemical demineralization, as well as phagocytic action. In a few cases, osteoblasts were seen adjoining osteoid seams with underlying calcified bone exhibiting frayed edges indicative of demineralization. Osteoclastic intranuclear inclusion bodies similar to those found in experimental lead poisoning were observed. It was considered that the presence of a frayed, calcified bone margin at a considerable distance from the osteoclast supports the proposition that the initial action of this cell is to demineralize calcified bone.

Animals↗
PubMed2026

ARID1A Mediates ROS-Induced Osteoclast Activation in TMJ Osteoarthritis.

Excessive osteoclast activation drives rapid subchondral bone destruction, serving as a critical early-stage event precipitating temporomandibular joint osteoarthritis (TMJ-OA). Although epigenetic remodeling is widely recognized as an important interface between pathological environmental signals and genomic response, the specific epigenetic mechanisms translating TMJ-OA-associated stimulation into pathological osteoclast activation remain to be elucidated. Here, using a mechanically induced TMJ-OA mouse model, we identify aberrant reactive oxygen species (ROS) accumulation as a critical upstream driver initiating excessive osteoclast activation and subsequent joint deterioration. By integrating transcriptomic and epigenomic analyses, we delineate the chromatin remodeler AT-rich interaction domain 1A (ARID1A) as an essential oxidative stress sensor within the osteoclast lineage. Mechanistically, ROS accumulation induces ARID1A upregulation and recruitment to the Src enhancer, transcriptionally activating Src and amplifying PI3K-AKT signaling to drive pathological osteoclastogenesis. Conditional knockout of Arid1a in myeloid cells effectively abrogates subchondral bone loss and cartilage destruction in TMJ-OA. Translating these mechanistic insights, we engineered an ROS-responsive, osteoclast-targeting hydrogel for the on-demand delivery of an ARID1A-dependent canonical BRG1/BRM-associated factor complex inhibitor, which successfully alleviates TMJ-OA progression. Our findings establish the epigenetic response to ROS accumulation as a key pathogenic mechanism in TMJ-OA and highlight ARID1A as a promising therapeutic target for early disease intervention.

biomaterial(s)↗
PubMed1979

The osteoclast-endothelium interface during bone resorption in the femurs of young rabbits.

The morphological between the osteoclasts at the endosteal surface of two-week-old rabbit femurs and the endothelium of vascular channels of the bone marrow was examined. Light microscopy revealed that 85% of the osteoclasts make direct contact with the endothelial cells. The ultrastructure of this osteoclast-endothelium interface shows that the osteoclast has specialized processes which reach towards the endothelial cells coming into proximity with them. On rare occasions, specialized junctions between these processes and the endothelial cells are noted.

Animals↗
PubMed1979

The occurrence of mononuclear cells at sites of osteoclastic bone resorption in experimental periodontitis.

The placement of silk ligatures around the necks of teeth and into the gingival sulcus causes a rapid, acute inflammatory response leading to vigorous osteoclastic resorption of alveolar crestal bone. Associated with the large numbers of osteoclasts are mononuclear cells, predominantly fibroblast-like cells and macrophages. Some fibroblast-like cells contain intracellular collagen fibrils. It is suggested that in periodontal disease these mononuclear cells may compliment the action of osteoclasts by ingesting and degrading matrix molecules mobilized from bone but not ingested or degraded by osteoclasts.

Alveolar Process↗
PubMed1979

Phagocytosis and trypsin-resistant glass adhesion by osteoclasts in culture.

Osteoclasts were cultured in vitro and tested for the functions normally associated with cells of the mononuclear phagocyte system. They were found to ingest glutaraldehyde-fixed red cells and latex, but not opsonised or complement-coated sheep red cells. Osteoclasts are glass-adherent and resist removal by trypsin. The implications of these findings for the identity of the osteoclast precursor cell and its mechanism of fusion are discussed.

Animals↗
PubMed1979

Monocytes regulate osteoclast-activating factor production by releasing prostaglandins.

Osteoclast-activating factor (OAF), a powerful stimulator of osteoclastic bone resorption, is released by peripheral blood mononuclear cells on exposure to phytohemagglutinin (PHA) or a specific antigen to which the leukocytes have been previously exposed. Both lymphocytes and monocytes are required in the leukocyte population for OAF release to occur. In this study we examined the relationship between the lymphocyte and monocyte in OAF production. Biological activity, as a result of OAF, was assessed by a bioassay based on the release of previously incorporated 45Ca from fetal rodent long bones in organ culture. We found that an enriched lymphocyte population depleted of monocytes by serial adherence does not release OAF after stimulation with PHA, although the cells are activated as assessed by [3H]thymidine and 3H-amino acid incorporation. When conditioned media harvested from adherent cells which did not contain OAF was added to the enriched lymphocytes, OAF release occurred. Media harvested from adherent cells which were cultured with indomethacin (10 microM), an inhibitor of prostaglandin synthesis, did not permit OAF release by activated lymphocytes. When PGE1 and PGE2 (0.1 microM) were added exogenously to the enriched lymphocyte population, OAF release occurred after stimulation with PHA. These results indicate that, (a) the activated lymphocyte is the cell or origin of OAF, (b) prostaglandins produced by monocytes are necessary for OAF production by activated lymphocytes, and (c) monocyte prostaglandins can influence bone resorption indirectly by regulating OAF production as well as directly by osteoclast activation. The interactions of OAF and prostaglandins at bone resorbing sites may be important in inflammatory and neoplastic diseases associated with bone destruction.

Bone Resorption↗
PubMed1979

The distribution of nuclei in imprints of feline osteoclasts.

Fresh imprints of metaphyseal bone from the femurs of four kittens aged 18 weeks were stained by histochemical methods for succinate, malate, beta-hydroxy butyrate, and glutamate dehydrogenases. In these preparations the unstained nuclei contrasted sharply with the background stained cytoplasm, making possible accurate nucleus counts in intact osteoclasts. The nuclei in 1683 osteoclasts were counted and the data revealed an asymmetric distribution of cells having different numbers of nuclei. The method may be of value in determining the precise significance of osteoclast size in relation to function.

Animals↗
PubMed1979

[Structural modifications of medullary bone osteoclasts during a hypocalcemic diet].

The medullary bone of laying hens after seven days of hypocalcaemic diet has been investigated with the aim of analyzing the fate of osteoclasts, very numerous in the first days of the diet and after substituted on the trabecular surfaces by active osteoblasts. The first observations show that there is a marked change in the osteoclasts ultrastructure. Large amount of endoplasmic granular reticulum in regular rows are accumulated at the cell periphery. Cytoplasmatic blebs, microvilli and laminae ondulantes are visible on the cell surfaces. Mononuclear cells with variable amount of cytoplasm rich in organuli are detached from osteoclasts. The ultrastructure and the fate of this elements are discussed.

Animals↗
PubMed1975

An unusual leiomyosarcoma of the uterus containing osteoclast-like giant cells.

An unusual variant of a poorly differentiated leiomyosarcoma of the uterus, containing osteoclast-like giant cells, is described. Areas of the resected tumor bore a close resemblance to giant cell tumor of bone. It is postulated that these giant cells, as well as the osteoclast-like giant cells reported in a number of tumors of other tissues, originate from the monocyte/histiocyte group of cells. The diagnosis of leiomyosarcoma was possible only after the tumor had been examined in the electron microscope. The ultrastructural features are consistent with a smooth muscle origin of the neoplasm; the final assessment is based on the relative proportions and frequency of such structures as: bundles of myofilaments with focal densities, marginal densities, pinocytotic vesicles, and an external lamina.

Cell Nucleus↗
PubMed1977

Osteopetrosis in the toothless (t1) rat: presence of osteoclasts but failure to respond to parathyroid extract or to be cured by infusion of spleen or bone marrow cells from normal littermates.

Osteoclast have been observe for the first time in toothless (t1) rats, a mutation with inherits osteopetrosis as an autosomal recessive. The ability of t1 rats to raise the serum calcium concentration after injection of parathyroid extract was severely limited when compared with normal littermates. In addition, osteopetrosis in t1 rats is not cured by radiation and infusion of normal spleen or bone marrow cells from normal littermates, a method know to cure osteopetrosis in mutants of this and other species. This indirect evidence for a reduction in bone resorption as a cause of osteopetrosis in this mutation and the failure of transplanted cells to cure the disease are discussed in relation to the development and function of osteoclasts.

Animals↗
PubMed1978

Enzyme histochemical properties of kitten osteoclasts in bone imprint preparations.

The enzyme histochemical characteristics of osteoclasts in imprints of the metaphyseal regions of femurs, from male kittens aged approximately 18 weeks, were investigated. A selected number of enzymes representative of a variety of metabolic pathways were studied. The enzyme profile, time for the first appearance of detectable reaction product, intensity of the reactions, and localization of the reaction products were noted. Osteoclasts are rich in enzymes, and metabolic pathways are well developed in respect of the utilization of the reduced coenzymes NADP and NADPH, succinic, malic, lactic, and isocitric acids, beta-hydroxybutyrate and glucose-6-phosphate, the reactions being mediated by the diaphorases and dehydrogenases. The activities of acid and neutral phosphatases, non-specific esterases, and leucine naphthylamidase were high in these cells. However, little or no activity was demonstrated in respect of glutamate and alpha-glycerophosphate dehydrogenases or of aryl sulphatase, glucose-6-phosphatase and alkaline phosphatase.

Animals↗