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S Niida

Publications and source records attributed to S Niida.

At least 19 recordsLinked to original sources

Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption.

We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was comparable to that of rhVEGF, showing that the VEGF signal is mediated through VEGFR-1. The rhM-CSF-induced osteoclasts died after injections of VEGFR-1/Fc chimeric protein, and its effect was abrogated by concomitant injections of rhM-CSF. Osteoclasts supported by rhM-CSF or endogenous VEGF showed no significant difference in the bone-resorbing activity. op/op mice undergo an age-related resolution of osteopetrosis accompanied by an increase in osteoclast number. Most of the osteoclasts disappeared after injections of anti-VEGF antibody, demonstrating that endogenously produced VEGF is responsible for the appearance of osteoclasts in the mutant mice. In addition, rhVEGF replaced rhM-CSF in the support of in vitro osteoclast differentiation. These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption.

Animals↗

Induction of hydroxyapatite resorptive activity in bone marrow cell populations resistant to bafilomycin A1 by a factor with restricted expression to bone and brain, neurochondrin.

Bone, one of the favored sites for tumor metastasis, is a dynamic organ undergoing formation and resorption. We found bone metastasis with osteolytic lesion in the bone marrow of the femur by injecting BW5147 T-lymphoma cells into the tail vein of AKR mice. To understand this bone destruction, we constructed a cDNA library from BW5147 with a cloning vector that allowed in vitro synthesis of mRNAs, and then identified a particular cDNA clone by adding the conditioned medium from Xenopus oocytes following injection of the mRNA synthesized in vitro to primary bone marrow heterogeneous cell populations on hydroxyapatite thin films. By means of this method, we isolated a factor with 16% leucine residues, termed neurochondrin, that induces hydroxyapatite resorptive activity in bone marrow cells resistant to bafilomycin A1, an inhibitor of macrophage- and osteoclast-mediated resorption. Expression of the gene was localized to chondrocyte, osteoblast, and osteocyte in the bone and to the hippocampus and Purkinje cell layer of cerebellum in the brain. This may provide insights into the molecular mechanisms underlying bone resorption with potential implications for the activation of cells other than macrophages and osteoclasts in bone marrow cells.

Amino Acid Sequence↗

Recruitment of osteoclasts in the mandibular condyle of growing osteopetrotic (op/op) mice after a single injection of macrophage colony-stimulating factor.

The purpose was to elucidate histological changes in the mandibular condyle and ramus in growing osteopetrotic (op/op) mice after a single injection of macrophage colony-stimulating factor (M-CSF). M-CSF (5 microg) was injected into 6-, 11-, 26-, 56- and 86-day-old op/op mice, and the mice were killed 4 days after the injection. In normal mice, the condyle was substantially wider than the ramus beneath it, and enlargement and ossification of the condyle occurred after weaning. These changes were not found in the uninjected and injected op/op mice, the condyles of which were occupied by hypertrophic cartilage cells, and the hypertrophic cell layer was thicker and more irregular in the arrangement of epiphyseal cell columns. In spite of the lack of bone resorption in uninjected and injected op/ op mice, ossification of the mandibular ramus occurred, but later than that of normal mouse. The number of tartrate-resistant acid phosphatase-positive cells in the injected op/op and normal mice approached a maximum at 30 days and then gradually decreased up to 90 days of age, although the numbers were substantially different for all ages. The uninjected op/op mice had no visible osteoclasts until 15 days and their number then increased significantly from 60 to 90 days of age. These results were considered due to the difference in biological responses of bony structures to M-CSF injection in the op/op mice. The influences of mechanical stimuli from masticatory functions, which are deficient in op/op mice, might also be responsible for the differences in bony architecture between the op/op and normal mice.

Animals↗

Suspension "hypokinesia/hypodynamia" may decrease bone mass by stimulating osteoclast production in ovariectomized mice.

This study was conducted to examine, in detail, the histological changes in the femurs of suspended ovariectomized (OVX) mice to assess the role of mechanical stress on bone remodeling. Suspended-OVX, suspended-sham-ope, nonsuspended-OVX, and nonsuspended-sham-operated mice underwent operations 8 weeks after birth. Immediately after operation, hypokinesia/hypodynamia was created by a suspension harness for one week. Five specimens in each group were sacrificed 9 weeks after birth. The trabecular bone of the femurs in the suspended-OVX mice was removed and replaced extensively by bone marrow. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was larger in the suspended-OVX mice than in the remaining three groups. No significant differences in the number of TRAP positive cells were found between the suspended-sham-ope, nonsuspended-OVX and nonsuspended-sham-ope mice. The femurs of the OVX mouse with suspension "hypokinesia/hypodynamia" thus exhibits extensive trabecular bone loss in association with an increase of osteoclasts.

Acid Phosphatase↗

Restoration of disturbed tooth eruption in osteopetrotic (op/op) mice by injection of macrophage colony-stimulating factor.

Osteopetrotic (op/op) mice show severe osteosclerosis caused by an inherited deficiency of osteoclast and resultant failure of tooth eruption, which can be cured by the injection of macrophage colony-stimulating factor (M-CSF). The present study revealed that consecutive injections of M-CSF in these mutant mice brought about a recovery of bone resorption resulting in the resumption of growth of tooth root and periodontal ligament. Bone resorption at the inner surface of bony crypts was noted on the 5th day after the start of M-CSF injections. This activity was reduced with the progress of root and periodontal ligament formation, being confined to the basal and crestal portion of bony crypts by the 15th day of the experiment. Second molars emerged into the oral cavity on the 15th day, but no eruption of first molars was observed until the 20th day. Throughout the experiment, first molars exhibited appreciable root deformity, which was less severe in second molars. Delayed eruption of first molars was thought to be related to the severity of the disturbance of root formation.

Age Factors↗

Selective extraction of beta-blockers from biological fluids by column-switching high-performance liquid chromatography using an internal-surface phenylboronic acid precolumn.

A column-switching HPLC method using an internal-surface phenylboronic acid precolumn for the selective extraction of beta-blockers from biological fluids has been developed. Filtered urine and plasma samples (50 microliters) were injected onto the precolumn equilibrated with methanol-0.05 M disodium hydrogenphosphate (5:95, v/v). After the precolumn had been washed briefly, the selectively retained beta-blockers were eluted with methanol-0.05 M phosphate buffer (pH 2.0) and transferred to a reversed-phase analytical column, on which they were then separated. Even after exposure to at least 160 injections of non-treated urine and plasma samples, the retention efficiency of the precolumn was maintained with no increase in back pressure. Quantitative recoveries and good reproducibility were demonstrated with pindolol.

Adrenergic beta-Antagonists↗

Development of the chondrocranial base of the musk shrew, Suncus murinus (Insectivora).

To reveal the developmental process of the chondrocranial base of the musk shrew, Suncus murinus (Insectivora), light microscopic observation of serial sections and macroscopic observation with whole-mount differential staining of bone and cartilage were performed on day-17 to -22 embryos. The following unusual findings were obtained: (1) The sphenoethmoidal commissure formed a part of the posterior edge of the tectum nasi, implying that the posterior portion of the paries nasi in the mammalian nasal capsule shares a common origin with the neurocranium. (2) The processus alaris arose independently from the hypophysial cartilage and also contributed to formation of the carotid foramen. (3) The hypophysial cartilage consisted of one medial and a pair of lateral cartilage nodules. The homology of the pair of cartilages with polar cartilages in lower vertebrates is discussed.

Animals↗

[Brain deformation caused by hyperplasia molar teeth (macrodonts) in the Japanese field vole (Microtus montebelli)].

Protrusion of hyperplastic upper molar teeth (macrodonts) into the cranial cavity was observed in the Japanese field vole. Protrusions of the upper molars occurred on both sides, but were large on the left than on the right. The teeth invaded the cranial cavity and brain parenchyma. Large concavities on the ventral side of the brain were interposed between the lateral olfactory tract and the optic tract. Invation by one macrodont reached the basal nuclei, hypothalamic and thalamic nuclei. The brain was deformed bilaterally, and nearly the entire olfactory bulb, globus pallidus, internal capsule, and lateral preoptic nucleus, and a portion of the hypothalamus, thalamus and anterior commissure were absent on the left side.

Animals↗

Expression of Mac-2 antigen in the preosteoclast and osteoclast identified in the op/op mouse injected with macrophage colony-stimulating factor.

Osteoclast deficiency in op/op mice is cured by a single injection of 5 micrograms recombinant human macrophage colony-stimulating factor (rhM-CSF). In this study, we found that mouse osteoclasts are positive for Mac-2 antigen, but not for F4/80, MOMA-2, Mac-1, or BM8 antigen. By using F4/80 and MOMA-2 monoclonal antibodies, we confirmed the absence of mature macrophages in the femora of op/op mice and found that multiple injections of rhM-CSF are required for the recruitment of macrophages in the bones. After a single rhM-CSF injection, we found Mac-2 positive mononuclear cells in the femora of op/op mice. The time course of the appearance of Mac-2-positive cells was very similar to that of tartrate-resistant acid phosphatase (TRAP)-positive cells. In bone sections prepared from the mutant mice that received rhM-CSF 3 days earlier, 91% of the TRAP-positive mononuclear cells were also positive for Mac-2 antigen. These results demonstrate the expression of Mac-2 antigen in preosteoclasts. The antigen was detected on the plasma membrane of preosteoclasts, as well as in their cytoplasm and nucleus, and in the extracellular matrix in the space between the cells and bone. Since Mac-2 is a galactose-specific lectin, a potential role of the lectin in cell-cell and cell-matrix adhesion during osteoclast differentiation is suggested.

Animals↗

Involvement of the c-kit receptor in the adhesion of hematopoietic stem cells to stromal cells.

The proto-oncogene c-kit, encoding a receptor-type tyrosine kinase, is allelic with the W locus of the mouse. The stromal cell line OP9, capable of supporting long-term hematopoiesis, was newly established from a newborn B6C3F1-op/op mouse calvaria. When bone marrow cells of WBB6F1-W/Wv mice were cocultured with the OP9 cells in liquid medium, hematopoiesis declined to a level one-thousandth of that in the cocultures of bone marrow cells of WBB6F1-+/+ mice and stromal cells by day 21. In contrast, when bone marrow cells of W/Wv mice were cocultured with OP9 cells in semisolid medium, at least 61% of the number of colonies were detected until the end of our observation period of 42 days when compared with that in control cocultures, although colonies formed by hematopoietic stem cells of W/Wv mice were significantly smaller than those of normal stem cells. After a 24-hour incubation with OP9 cells, fewer stem cells of W/Wv mice than normal ones adhered to the stromal cells. Adhesion of normal stem cells to stromal cells was inhibited by the addition of an antagonists anti-c-kit monoclonal antibody, ACK2. These results demonstrate that the c-kit receptor plays an important role not only in the proliferative response of hematopoietic stem cells but also in their adhesion to stromal cells.

Animals↗

Occipital roof development in the Japanese musk shrew, Suncus murinus.

The occipital squama of the Japanese musk shrew, Suncus murinus, consists only of membrane bone which arises from the periosteal bony band of the supraoccipital cartilage. No cartilaginous tectum posterius, generally forming the dorsal border to the foramen magnum, was found in the developing chondrocranium. Also additional intramembranous ossification centres were occasionally observed, and could be interpreted as being the primordium of the interparietal bone. These observations indicate that the membrane bone is homologous not with the interparietal bone but with the tectum posterius, i.e. the membranous supraoccipital bone. This is an instance of interchangeability between cartilage and membrane bone in a mammal.

Animals↗

Sexual dimorphism in the trigeminal motor neurons innervating the mouse masseter muscle.

The extrafusal and intrafusal muscle fibers in the masseter muscle are innervated by motoneurons in the trigeminal motor nucleus (Mo 5). In the present study, we found that the number of trigeminal motor neurons in the male mouse was significantly larger than that in the female. However, we could not detect any significant difference between male and female mice in the number of sensory neurons in the trigeminal mesencephalic nucleus (Me 5). This is the first report on sexual dimorphism in masticatory motoneurons of mammals.

Animals↗

Functional combination of tapering profiles and overlapping arrangements in nonspanning skeletal muscle fibers terminating intrafascicularly.

Using digital image analysis and several anatomical methods, morphometric analysis of nonspanning fibers which had tapering profiles at their intrafascicular termination sites and represented overlapping arrangements within the fiber fascicles was performed in the rat rectus abdominis. Special emphasis was focused on dimensional relationships occurring between overlapping portions and tapering segments and sarcomere lengths in non- and overlapping portions. Nonspanning fibers were found to overlap each other for more than 40% of their length. In length, their overlapping portions generally corresponded to their tapering segments, which were also greater than 40% of the fiber length. In addition, despite the presence of overlapping linkages, nonspanning fibers maintained a fairly uniform length irrespective of their overlapping and nonoverlapping portions. Overlapping linkages in fibers without tapering profiles have a larger cross-sectional area in the overlapping portion than in the non-overlapping one, resulting in a phenomenon which will cause different sarcomere lengths between the two portions during fiber stretching. The present results suggest that tapering profiles in the overlapping portion ensure uniform sarcomere lengths within nonspanning fibers, thereby providing mechanical stability in each fiber.

Abdominal Muscles↗

Transient recruitment of osteoclasts and expression of their function in osteopetrotic (op/op) mice by a single injection of macrophage colony-stimulating factor.

Severe deficiency of osteoclasts in op/op mice, caused by the absence of functional macrophage colony-stimulating factor (M-CSF), is cured by daily injections of purified recombinant human M-CSF (rhM-CSF). In this study, we found that a single injection of 5 micrograms rhM-CSF is enough for recruitment of osteoclasts in mutant mice. Osteoclast number increased during the period between 2 and 4 days after the single rhM-CSF injection. When YM175, a new derivative of bisphosphonate, was administered to the mice 4 days after rhM-CSF injection or later, osteoclasts disappeared by 3 days after YM175 administration. However, a significant number of osteoclasts were detected even at 3 days after YM175 administration when YM175 was administered 3 days after rhM-CSF injection or earlier. These results indicate that YM175 is cytotoxic only to functioning osteoclasts and that recruitment of osteoclasts is finished 4 days after a single rhM-CSF injection. The osteoclasts actively resorbed bone trabeculae for a prolonged period, demonstrating that M-CSF is not requisite for the functioning of mature osteoclasts.

Animals↗

Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells.

Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.

Acid Phosphatase↗

Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor.

Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and peritoneal macrophages because of a defect in the production of functional macrophage colony-stimulating factor (M-CSF) resulting from a mutation within the M-CSF gene. In this study, we examined whether daily 5-microgram injections of purified recombinant human M-CSF (rhM-CSF) for 14 d would cure these deficiencies in the mutant mice. Monocytes in the peripheral blood of the op/op mice were significantly increased in number after subcutaneous injections of the factor two or three times a day. In contrast, osteopetrosis in the long bones of op/op mice was completely cured by only one injection of rhM-CSF per day. Bone trabeculae in the diaphyses were removed. Many osteoclasts were detected on the surface of bone trabeculae in the metaphyses. Although development of tooth germs of uninjected op/op mice was impaired, rhM-CSF injection restored the development of molar tooth germs and led to tooth eruption as a consequence of the recovery of bone-resorbing activity. These results demonstrate that M-CSF is one of the factors responsible for the differentiation of osteoclasts and monocyte/macrophages under physiological conditions.

Animals↗