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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↗
PubMed1977

Osteoclast counting in crista biopsies.

A description is given of a modified method of counting osteoclasts both per section area and also relative to the remaining trabeculae surface area in crista biopsies. The material consisted of normal individuals, patients with clinical osteoporosis, and patients with chronic renal failure undergoing haemodialysis. The number of osteoclasts in the biopsies from normal and osteoporotic individuals showed a normal distribution with the same mean. In the haemodialysis patients there was a marked skew distribution. In normal individuals, there was a significant decrease in the number of osteoclasts per section area with age, but this was not significant when calculated relative to the bone surface area.

Adolescent↗
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↗
PubMed1978

beta-Hydroxybutyrate dehydrogenase activity in human and kitten odontoclasts and kitten osteoclasts.

beta-Hydroxybutyrate dehydrogenase activity was studied in whole cell preparations of human and kitten odontoclasts and kitten osteoclasts. Strong histochemical reactions occurred within 2--10 min in all three giant cell types. The possible significance of the high levels of beta-hydroxybutyrate dehydrogenase activity in the metabolism of odontoclasts and osteoclasts is discussed.

Animals↗
PubMed1979

Timing of indomethacin in the control of prostaglandins, osteoclasts and bone destruction produced by VX2 carcinoma in rabbits.

Rabbits were injected with VX2 cancer cells into the left thigh or tibia, and given indomethacin 1-16 mg/kg daily starting on the day before tumour implantation or 7, 14 or 21 days after implantation. Indomethacin at 2 mg/kg and above from before tumour implantation reduced osteoclast proliferation and the amount of prostaglandin-like material extracted from homogenates of excised tumours, but the inhibition of bone destruction in vivo was significant only with indomethacin at 4 mg/kg and above. Indomethacin at 8 mg/kg reduced osteoclast proliferation and bone destruction, but the effect was statistically significant only when given within 7 days of inoculation with the tumour. The place of indomethacin and other inhibitors of prostaglandin synthesis has not yet been established in the management of patients with skeletal metastases. Drug administration might need to be started at the time of diagnosis and removal of the primary tumour, rather than when skeletal metastases are evident.

Animals↗
PubMed1979

Mammary carcinoma with osteoclast-like giant cells. A study of eight cases with follow-up data.

Eight cases of a rare, distinctive variant of infiltrating mammary carcinoma featuring benign multinucleated osteoclast-like giant cells are reported. The multinucleated osteoclast-like giant cells are reported. The multinucleated giant cells were associated with ductal carcinoma in five cases and with infiltrating lobular carcinoma in three cases. Although three patients had lymph nodal metastases in level one, none of the nodal metastases contained giant cells. From the limited follow-up data of this report, it seems likely that the prognosis for patients who have this type of adenocarcinoma is not especially favorable. The observation that the giant cells generally occurred in areas of prominent angiogenesis suggests that the angiogenesis may be induced by some chemical substance produced by the tumor cells. Biochemical and immunologic investigations may eventually provide an explanation for this unusual morphologic manifestation of host reaction to mammary carcinoma.

Adult↗
PubMed1977

1,25-dihydroxycholecalciferol and parathormone: effects on isolated osteoclast-like and osteoblast-like cells.

The actions of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and parathormone, both effective bone-resorptive agents in vivo and in vitro, were tested on CT (osteoclast-like) and PT (osteoblast-like) bone cells maintained in culture. Both agents stimulated acid phosphatase activity and hyaluronate synthesis in the CT cells and decreased alkaline phosphatase, citrate decarboxylation, and collagen synthesis in the PT cells. Calcitonin inhibited the changes induced in the CT but not in the PT cells. The activity of 1,25-(OH)2D3 differed from that of parathormone in one key respect: it did not increase cellular cyclic adenosine monophosphate, whereas parathormone did. Prior incubation of the bone cells with 1,25-(OH)2D3 for 6 to 24 hours made the cells refractory to the effect of parathormone on cyclic adenosine monophosphate formation. These data suggest that 1,25-(OH)2D3 and parathormone induce bone resorption by affecting the same cell types (osteoblasts and osteoclasts) although at different cellular sites.

Acid Phosphatase↗
PubMed1979

Induction of metabolic changes and down regulation of bovine parathyroid hormone-responsive adenylate cyclase are dissociable in isolated osteoclastic and osteoblastic bone cells.

Bovine parathyroid hormone (PTH), dibutyryl cAMP, and calcium each induce similar metabolic changes in isolated bone cells. PTH and calcium, but not dibutyryl cAMP, result in desensitization of osteoclastic and osteoblastic bone cells to PTH. In osteoblastic cells, calcium effects are specific for PTH receptor.adenylate cyclase complexes and responsiveness to other hormones is not reduced while in osteoclastic cells, small effects of high calcium on prostaglandin E1- and epinephrine-inducible cAMP accompany the large decreases seen in cAMP response to PTH. The membrane effects of calcium and of PTH appear to be independently regulated as PTH-induced desensitization can be initiated in the absence of calcium. In addition, calcium effects on PTH-sensitive adenylate cyclase follow a different calcium dose-response than PTH-like metabolic changes. These results suggest that the effect of calcium on the membrane is not directly related to its induction of PTH-like metabolic changes. A possible role of calcium as an in vivo regulator of bone cell sensitivity to PTH is discussed.

Adenylyl Cyclases↗
PubMed1979

[Demonstration by immunofluorescence and immunoperoxidase of an antigen of the measles type in the osteoclasts of Paget's disease of bone].

The intra nuclear and intra cytoplasmic inclusions described in osteoclasts in PAGET's bone disease are morphologically similar to those observed in subacute sclerosing panencephalitis. Immunological techniques using different specific immune sera demonstrate the presence of an antigenic structure of viral origin in osteoclasts in PAGET's bone disease. A measles or a measles like virus is most likely to be involved and may play a role in the etiology of the disease.

Antigens, Viral↗
PubMed1979

Skeletal changes during prolonged external irradiation: alterations in marrow, growth plate and osteoclast populations.

This report describes hematologic and skeletal changes in young mice subjected to continuous external whole body irradiation (45 rads/day) for 4 days to 12 weeks. Irradiation caused a rapid depletion of hematopoietic stem cells, marrow aplasia and pancytopenia, all of which persisted during the period of irradiation but resolved afterward. In spite of suppressed cellular proliferation and disarray of cartilage cell columns in metaphyseal plates, linear bone growth appeared to continue at physiologic rates. Histologic and morphometric studies provided no evidence of impaired osteoblast function, but the presence of thickended trabeculae beneath the growth plate and of cartilagenous islands within cortical shafts of long bones indicated that bone remodeling was deficient. Direct osteoclast counts demonstrated that marrow aplasia was followed by a progressive decline that could not be reversed by parathormone injections or infusions with mature macrophages and lymphocytes but that resolved once the bone marrow recovered following cessation of irradiation. Therefore, the altered bone remodeling probably resulted from radiation injury to osteoclast precursors in the hematopoietic compartment.

Animals↗
PubMedDate not supplied

[Induced hypocalcaemia test using salmon calcitonin as a means for the evaluation of osteoclastic activity (author's transl)].

The authors measured the degree of hypocalcaemia (delta Ca S), hypophosphataemia and the fall in urinary hydroxyproline excretion induced by an intramuscular injection of 100 MRC U of synthetic salmon calcitonin (S.C.T.) during the 24 hours following the injection. In 15 control subjects, the fall in plasma calcium was slight ( - 2.1 +/- 0.9 mg/l) but significant. In bone diseases involving hyperosteoclastosis, the degree of hypocalcaemia was much greater: 10.6 +/- 1.1 mg/l in 24 cases of Paget's disease, - 9.0 +/- 1.6 mg/l in 5 cases of diffuse malignant disease of bone, - 8.0 +/- 1.4 mg/l in 6 cases of primary hyperparathyroidism and - 3.5 +/- 0.8 mg/l in 13 cases of algodystrophy of the limbs. In the subjects studied as a whole there was a significant linear relationship between the delta Ca S and the extent of the trabecular surfaces of osteoclastic resorption, but not between delta Ca S and total 24 hour urinary hydroxyproline excretion. The S.C.T. hypocalcaemia test would appear to be a simple means for the evaluation of osteoclastic activity within the skeleton, and thus to select those bone disorders which should respond to antiosteoclastic therapy (calcitonin, diphosphonates).

Adult↗
PubMedDate not supplied

The ultrastructure of the osteoclast and its functional implications.

Recent findings on the ultrastructure of the osteoclast indicate that special attention should be given to the ruffled border, clear zone, and the vacuoles and vesicles of the cell and their significance for the mechanism of breakdown of bone matrix. The ruffled border is seen as an extensive area of cell surface where secretion of enzymes as well as uptake of matrix components takes place. The clear zone encircles the ruffled border completely and thus forms an integral part of the resorbing apparatus. Vacuoles and vesicles are thought to secret enzymes as well as take up extracellular material and possible digest or transport these products in the cell. The changes that occur in the ultrastructure of the osteoclast after exposure to parathyroid hormone and calcitonin indicate an important role of the ostioclast in bone metabolism. The cell can increase its activity very rapidly in response to parathyroid hormone, and decrease its activity in response to calcitonin.

Bone and Bones↗