PubMed Health⌕ Search

Biomedical subjects

J Tuukkanen

Publications and source records attributed to J Tuukkanen.

15 recordsLinked to original sources
PubMed1995

Effects of recombinant human osteogenic protein-1 on the differentiation of osteoclast-like cells and bone resorption.

Recombinant human OP-1 stimulated the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) significantly and in a dose-dependent manner in rat bone marrow cell culture. Newly formed MNCs either induced by hOP-1 alone or with 1,25(OH)2D3 were also positive for vitronectin receptor and carbonic anhydrase II. Moreover, OP-1 markedly increased the capacity of 1,25(OH)2D3 to induce osteoclast-like cell formation and bone resorption in bone marrow cultures. 25 pg/ml of calcitonin significantly inhibited both OP-1- and vitamin D3-induced TRAP-positive MNC-formation in marrow cultures, indicating that in both cases the MNC formation was calcitonin sensitive. OP-1 at 5-100 ng/ml did not have any significant effect on bone resorption as studied by pit formation assay. These studies that OP-1 in concert with 1,25(OH)2D3 could have an important role in bone remodeling by exhibiting its effects not only on osteoblast growth and differentiation but also on the recruitment of osteoclasts.

Actins↗
PubMed1995

Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages.

A novel murine plasma membrane protein has been identified in subpopulations of macrophages. It has an intracellular N-terminal domain, a transmembrane domain, and an extracellular region with a short spacer, an 89 Gly-Xaa-Yaa repeat-containing collagenous domain, and a C-terminal cysteine-rich domain. In situ hybridization and immunohistochemical staining have localized the protein to a subset of macrophages in the marginal zone of the spleen and the medullary cord of lymph nodes. No expression was observed in macrophages of liver or lung. Transfected COS cells synthesized a native trimeric plasma membrane protein that bound labeled bacteria and acetylated LDL, but not yeast or Ficoll. The results suggest that the novel protein is a macrophage-specific membrane receptor with a role in host defense, as it shows postnatal expression in macrophages, which are considered responsible for the binding of bacterial antigens and phagocytosis.

Amino Acid Sequence↗
PubMed1994

Exercise can provide protection against bone loss and prevent the decrease in mechanical strength of femoral neck in ovariectomized rats.

The effect of treadmill exercise on bone loss in ovariectomized (OVX) rats was studied in two different sets of experiments. In the first experiment rats were either ovariectomized (n = 38) or sham operated (n = 18) at the age of 12 weeks. Half the OVX rats were trained twice a day for 30 minutes by running at 10 m/minute for 7 or 17 weeks. In the second experiment 40 female rats, aged 12 weeks, were divided into five groups (n = 8). One group of rats was sacrificed on day 0 for the baseline data. Other rats were sham operated or ovariectomized for 9 weeks. Half of both groups were trained using the same training program as in the first experiment. OVX reduced trabecular bone volume (TBV) in the distal femur to 42.7 and 48.3% in 8 and 18 weeks, respectively. Exercise opposed this effect significantly but could not prevent it totally. Exercise did not have any significant effect on sham-operated animals. OVX induced a 17.7 and 30.7% decrease in maximal failure load of femoral neck in 8 and 18 weeks, respectively. A corresponding decrease was also observed in the torque capacity of tibia. Exercise was able to prevent almost totally the decrease in bone strength of femoral neck, tibia, and humerus. In conclusion, our results suggest that the measurement of bone strength in aging female rat femoral neck can be used as a useful indicator of the deleterious effect of OVX in bone. These results further indicate that exercise can overcome a significant part of the decrease in trabecular bone volume and maintain the mechanical strength of femoral neck and tibial shaft in the OVX rats.

Analysis of Variance↗
PubMed1994

Effect of running exercise on the bone loss induced by orchidectomy in the rat.

The effect of exercise on castration-induced osteoporosis in 3-month-old male rats weighing 264 +/- 4 g at the beginning of the experiment was studied. A testosterone deficiency was induced by orchidectomy (ORC), and the exercise group ran 10 m/minute for 1 hour a day on a treadmill at 0% grade. There were seven groups of eight rats (n = 56) randomized into a control group killed at time 0, and sham, ORC and ORC and exercise groups killed at 4 and 8 weeks. ORC reduced body weight gain (with analysis of variance (ANOVA) P < 0.001), and at 4 weeks the body weight was 343 +/- 14 g in ORC group and 301 +/- 4 g in the ORC and exercise group (P < 0.01). The increase in femoral length was slower in the ORC+exercise groups. The ash weight of the tibia did not decrease significantly after ORC or ORC+exercise. ORC did not affect 45Ca incorporation, but exercise slightly increased it in the whole tibia 8 weeks after ORC (with ANOVA P = 0.057). ORC had significantly lowered the trabecular bone volume in the secondary spongiosa of the distal femur at 4 and 8 weeks, and exercise did not prevent this. This is an opposite finding to our previous study with ovariectomized female rats [12]. ORC also significantly had reduced the osteoblast-lined trabecular bone surface and the number of osteoclasts by 8 weeks after the operation. Exercise increased the osteoblast-lined surface and the number of osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

The effect of training on the recovery from immobilization-induced bone loss in rats.

We studied the effect of exercise on the recovery from osteoporosis induced by immobilization in growing laboratory rats. The right hind limb of male rats was immobilized by cast for 2 weeks. The rats were then divided into control and exercise groups. The controls were allowed to move freely in their cages and the exercise group was running for 1 hour every day. After 2 weeks immobilization, the ash weight of the immobilized tibia decreased to 85.2 +/- 0.6% (P less than 0.001) from that of contralateral tibia. After removal of the cast, the bone mass recovered and, in 9 weeks, the decrease of ash weight was reduced to 2.9 +/- 0.8% and 4.2 +/- 0.3% in the control and exercise groups, respectively. There was no statistical difference in ash weights between the running and control groups and the trabecular bone volume in the distal femur was also equal in both groups. Immobilization reduced the incorporation of [45Ca] into the tibia. After remobilization, the [45Ca]-incorporation was found to be significantly higher in the recovering leg than in the control leg. Exercise further stimulated [45Ca]-incorporation into the recovering tibia.

Animals↗
PubMed1991

Changes induced in growing rat bone by immobilization and remobilization.

We studied changes in bone mass and histology in growing rats after different relatively short periods of immobilization and during subsequent remobilization. Immobilization-induced loss of bone weight is mainly due to mineral losses as indicated by changes in wet weight, ash weight, and calcium content. 45Ca2+ incorporation was found to be decreased in immobilized bones and showed strong dependence upon the age of the rats. Histological examination showed rapid and extensive trabecular bone loss, and external measurements of bone length and diameter confirmed that a substantial part of the decrease in bone mass was due to actual trabecular bone loss and not the reduction of external bone volume. Two of the methods studied, cast immobilization and reversible neurectomy, allow subsequent remobilization and thus enable recovery of the bone to be studied. Bone ash weights were 12.3 +/- 1.12% and 13.1 +/- 1.82% below the control values in the tibia and the femur, respectively, after three weeks of cast immobilization and 12.0 +/- 1.10% and 9.2 +/- 0.90% below after three weeks of immobilization by reversible neurectomy. The bone mineral mass recovered by 40% (p less than 0.053) in the femur and 67% (p less than 0.027) in the tibia during the three weeks' remobilization following one week of cast immobilization, and 62% (p less than 0.001) in the tibia but only 38% (p less than 0.073) in the femur after three weeks of cast immobilization. Mobility of the extremity was restored after three weeks of immobilization by reversible neurectomy, whereupon about half of the lost bone mass was recovered in both the tibia and the femur during six weeks of reinnervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Calcitonin treatment of immobilization osteoporosis in rats.

We studied changes in bone mass induced by immobilization and the ability of salmon calcitonin to inhibit immobilization osteoporosis in rat. The bone mass of the immobilized hind leg of rat was compared with the contralateral non-treated leg. Neurectomy and cast immobilization reduced the bone mineral mass to an equal extent. However, the dose-response of calcitonin was different with these immobilization techniques. Calcitonin 15 IU kg-1 administered once daily reduced bone ash weight difference significantly after 2 weeks' neurectomy (P less than 0.001). This had no significant effect on the bone loss induced by cast immobilization, but the dose had to be delivered as two injections given every 12 h. Two weeks' immobilization decreased the incorporation of 45Ca into bones. Calcitonin could not prevent this. However, calcitonin tended to inhibit the overall incorporation of 45Ca into bones in immobilized rats but yet had no effect on 45Ca incorporation in non-immobilized rats. Immobilization decreased serum alkaline phosphatase activity in cast-immobilized animals. Neurectomy did not change serum alkaline phosphatase activity from a sham operation level. The tartrate-resistant acid phosphatase to total acid phosphatase ratio in the serum increased significantly in neurectomized rats and in cast-immobilized calcitonin-treated rats.

Alkaline Phosphatase↗
PubMed1990

Osteoclasts and a small population of peripheral blood cells share common surface antigens.

Several methods have been tried to identify mononuclear osteoclast precursors. We used a panel of 13 osteoclast-recognizing monoclonal antibodies (mabs) for the identification of osteoclast precursor cells from the bone, bone marrow, and peripheral blood of egg laying hens. Almost all mabs stained some mononuclear cells in the bone. Seven mabs recognized few mononuclear cells in the bone marrow and five mabs gave the positive immunofluorescence reaction in the white blood cell fraction. Possible immediate osteoclast precursor cells differing from osteoclasts in their densities were identified in the bone. Three mabs (K38, K52, and K70) stained the same amount of mononuclear cells (2.6-3.4%) enriched in Percoll density centrifugation. Of the monoclonal antibodies that recognized few cells in blood, K41 stained only osteoclasts. K47 and K52 also recognized some mononuclear cells in the bone marrow. Other monoclonal antibodies K51 and K70 were more unspecific, since they stained cells derived from other tissues. Blood cells detected with these different monoclonal antibodies were negative for tartrate-resistant acid phosphatase (TRAP). On the basis of our results, we suggest that there is in the blood a specific TRAP-negative cell population, which is a good candidate for osteoclast precursor.

Animals↗
PubMed1990

Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts.

Microsomal membrane vesicles prepared either from chicken medullary bone or isolated osteoclasts were shown to have ATP-dependent H(+)-transport activity. This activity was N-ethylmaleimide-sensitive but resistant to oligomycin and orthovanadate, suggesting a vacuolar-type ATPase. Furthermore, immunological cross-reactivity of 60- and 70-kD osteoclast membrane antigens with Neurospora crassa vacuolar ATPase was observed when analyzed by immunoblotting. Same antibodies labeled only osteoclasts in chicken and rat bone in immunohistochemistry. Immunoelectronmicroscopy localized these antigens in apical membranes of rat osteoclasts and kidney intercalated cells of inner stripe of outer medulla. Pretreatment of animals with parathyroid hormone enhanced the immunoreaction in the apical membranes of osteoclasts. No immunoreaction was seen in osteoclasts when antibodies against gastric H+,K(+)-ATPase were used. These results suggest that osteoclast resorbs bone by secreting protons through vacuolar H(+)-ATPase.

Animals↗
PubMed1989

Organization of osteoclast microfilaments during the attachment to bone surface in vitro.

Rat and chicken osteoclasts were cultured on bone slices, where they showed active resorption with resorption lacunae, which cold be seen by toluidine blue staining or with a scanning electron microscope. Osteoclast microfilaments, F-actin, vinculin, and talin were studied by immunofluorescence. In attached osteoclasts, vinculin appeared as a double circle in the periphery of the cell, and the most intense F-actin staining was located between these vinculin zones. Some chicken osteoclasts showed also intense F-actin staining throughout the center of the cell. Talin appeared in a similar double circle to vinculin. This kind of distribution of microfilaments was always associated with resorption lacunae, and F-actin, vinculin, and talin zones correspond roughly to the edge of lacunae. Osteoclasts showing a diffuse staining pattern were not associated with a resorption pit. The results suggest that this specific microfilament arrangement is located at the attachment zone of the osteoclast and is obligatory for the attachment and resorption. However, this arrangement of microfilaments is quite different from the one that has been previously described in osteoclasts cultured on glass.

Acid Phosphatase↗
PubMed1988

Mechanism of osteoclast mediated bone resorption.

The osteoclast is the main bone resorbing cell. It has several structural features which are related to its function. In active resorption stage this multinucleated giant cell shows remarkable polarity which, with its basolateral and apical membrane surfaces, resembles a secreting epithelial cell. The third specialized membrane area, sealing zone, mediates the attachment of the osteoclast to the bone surface. The rate of bone resorption can be regulated either by changing the number or the activity of resorbing osteoclasts. These processes can be influenced by different systemic circulating factors as well as local, bone matrix or other bone cell-derived factors. After activation of stem cells, preosteoclasts are guided to the bone surface where they undergo fusion into multinucleated osteoclasts. A special type of cell attachment to mineralized bone surface precedes actual resorption process. During cell attachment cytoskeletal structures are organized into a typical belt-like structure. The actual attachment receptor as well as its counterpart in bone matrix are not yet known. Bone mineral dissolution is then initiated by active secretion of H+ through the ruffled border membrane area. Acidification of the resorption lacuna together with hydrolytic enzymes completes finally the degradation of organic matrix of bone.

Bone Matrix↗
PubMed1986

Identification of osteoclasts by rhodamine-conjugated peanut agglutinin.

Rhodamine-conjugated Arachis hypogaea (peanut agglutinin, PNA) lectin, which is specific for beta-D-galactosyl and beta-D-gal-[1,3]-D-galNAC residues, was used to identify osteoclasts in paraffin-embedded bone sections of fetal rat calvaria and a human bone-derived tumor, osteoclastoma. All multinucleated osteoclasts were positive for PNA-lectin. This was also confirmed by studying smears of isolated osteoclasts from rat and chicken long bones. In addition to multinuclear cells, some mononuclear cells on the endosteal surface of the rat calvaria and some bone marrow cells also revealed specific binding of PNA lectin. Isolated rat peripheral monocytes were also studied, and these showed specific binding of PNA lectin which was maintained unchanged for at least 3 days in culture. Different lectins could be useful as membrane markers for studying bone cell origin and maturation.

Animals↗
PubMed1986

Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro.

Omeprazole has been previously shown to block gastric acid secretion by specific inhibition of gastric parietal cell membrane H+-K+-ATPase. It is now demonstrated that similar concentrations of omeprazole will inhibit PGE2- and PTH-stimulated 45Ca++ release from prelabelled neonatal mouse calvariae without affecting the viability of cultured calvaria explants.

Adenosine Triphosphatases↗
PubMedDate not supplied

The mechanical strength of bone in different rat models of experimental osteoporosis.

In order to discover good parameters for experimental osteoporosis, we measured the failure load of the femoral neck and the bending strength of the tibia in orchidectomized (ORC) (20 rats for 4 weeks), ovariectomized (OVX) (28 rats for 6 weeks), and immobilized (IMM) (33 rats for 3 weeks) rats. Each of these operations led to a significant decrease in trabecular bone volume when compared with corresponding controls (p < 0.001). The ash weight of femurs was significantly decreased in ORC (p < 0.05) and IMM (p < 0.001) rats, but not in OVX rats. Growth of the femur was somewhat slower in ORC (p < 0.05) and IMM rats (p < 0.05), but not in OVX animals. All three osteoporosis models showed significant decreases in the maximal load of the femoral neck (ORC: 23.9%, p < 0.001; OVX: 15.8%, p < 0.001; IMM: 27.7%, p < 0.001), as well as in energy absorption (ORC: 43.9%, p < 0.001; OVX: 28.3%, p < 0.001; IMM: 45.3%, p < 0.001). In tibia orchidectomy reduced maximal strength and energy absorption significantly (10%, p < 0.01; 27.8%, p < 0.01), but ovariectomy decreased only maximal load (8.7%, p < 0.01) and immobilization only energy absorption (18.0%, p < 0.01). Our results suggest that the mechanical strength of the femoral neck is a sensitive indicator of bone loss in all three osteoporosis models.

Animals↗