Indirect visualization of hematopoietic colony-forming stem cell (CFUs) as a possible target cell for Mycoplasma arthritidis

Utilizing specific rabbit antiserum against M. arthritidis together with complement, a portion of the marrow 7-day CFUs population of CBA mice infected with live mycoplasma organisms 1 day previously was shown to be inactivated. These cells might therefore be considered as candidate target cells for M. arthritidis. 11-day CFUs were unaffected by similar treatment.     

Indirect visualization of hematopoietic colony-forming stem cell (CFUs) as a possible target cell forMycoplasma arthritidis

Summary Utilizing specific rabbit antiserum againstM. arthritidis together with complement, a portion of the marrow 7-day CFUs population of CBA mice infected with live mycoplasma organisms 1 day previously was shown to be inactivated. These cells might therefore be considered as candidate target cells forM. arthritidis. 11-day CFUs were unaffected by similar treatment.     

Cell proliferation in the bone marrow and thymus following partial bone marrow aspiration

Summary Aspiration of the one femoral bone marrow caused a significant rise of the cell population, arrested in colchicine-metaphase both of the bone marrow from the other femur and of the thymus.     

Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice

Bone marrow stroma produces positive and negative growth regulators which constitute the hematopoietic microenvironment. As many tumors metastasize to the bones, these regulators may also influence tumor growth. Hematopoietic cytokines may indeed exert both positive and negative effect on tumor growth. We report that, when mixed with tumor cells. adherent bone marrow cells inhibit primary tumor growth and metastases formation in mice transplanted with Lewis lung carcinoma or B16 melanoma. Peritoneal macrophages or lymph node cells did not exert any influence. The tumor inhibition was apparently due to soluble factor(s) released by marrow stromal cells. In cocultures with B16 melanoma cells, adherent bone marrow cells exerted a significant antiproliferative effect which was increased by previous culture of the bone marrow cells with granulocyte-macrophage colony-stimulating factor but not with macrophage colony-stimulating factor. Neither neutralizing antibodies against tumor necrosis factor-alpha, transforming growth factor-beta or interferon alpha/beta nor addition of Escherichia coli lipopolysaccharide to generate inflammatory cytokines could affect the antiproliferative effect of bone marrow stromal cells. The bone marrow stroma factor(s) which inhibit tumor growth might, therefore, be a novel growth regulator.     

The p38α MAPK positively regulates osteoblast function and postnatal bone acquisition

Bone continuously remodels throughout life by coordinated actions of osteoclasts and osteoblasts. Abnormalities in either osteoclast or osteoblast functions lead to bone disorders. The p38 MAPK pathway has been shown to be essential in controlling osteoblast differentiation and skeletogenesis. Although p38α is the most abundant p38 member in osteoblasts, its specific individual contribution in regulating postnatal osteoblast activity and bone metabolism is unknown. To elucidate the specific role of p38α in regulating osteoblast function and bone homeostasis, we generated mice lacking p38α in differentiated osteoblasts. Osteoblast-specific p38a knockout mice were of normal weight and size. Despite non-significant bone alterations until 5?weeks of age, mutant mice demonstrated significant and progressive decrease in bone mineral density from that age. Adult mice deficient in p38a in osteoblasts displayed a striking reduction in cancellous bone volume at both axial and appendicular skeletal sites. At 6?months of age, trabecular bone volume was reduced by 62?% in those mice. Mutant mice also exhibited progressive decrease in cortical thickness of long bones. These abnormalities correlated with decreased endocortical and trabecular bone formation rate and reduced expressions of type 1 collagen, alkaline phosphatase, osteopontin and osteocalcin whereas bone resorption and osteoclasts remained unaffected. Finally, osteoblasts lacking p38α showed impaired marker gene expressions and defective mineralization in vitro. These findings indicate that p38α is an essential positive regulator of osteoblast function and postnatal bone formation in vivo.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early, in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocytemacrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of houng adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed, and/or were first to recover, even during continued drug exposure.     

Age-related differences in the effect of in vivo administration of indomethacin on hemopoietic cell lineages of the spleen and bone marrow of mice.

During 21 days of indomethacin treatment, erythroid cells in the spleens of both young adult and older mice, and in the bone marrow of young adult mice, were increased significantly early in treatment, relative to age-matched control organs, and remained high throughout treatment. During drug exposure, the numbers of myeloid cells in young adult bone marrow, but not spleen, were reduced, but in older mice these cells were elevated in both organs. Lymphoid cells in the young adult and older mouse spleens decreased and increased, respectively, during treatment, but were unchanged and decreased, respectively, in the bone marrow of young adult and older mice. Monocyte-macrophage cells in the spleen were elevated but unchanged in the bone marrow of both age groups. During 14 days of indomethacin treatment of young adult mice, the proportions of precursor cells in DNA synthesis of only the splenic erythroid lineage were increased. Thus, the major hemopoietic lineages in both the bone marrow and spleen are affected by exposure to indomethacin in a time-dependent and age-dependent manner. For all lineages studied, those of the bone marrow were least disturbed and/or were first to recover, even during continued drug exposure.     

Imparied bone resorption of cultured calvaria from mice with abnormal lysosomal function (the Chediak-Higashi syndrome)

Summary Spontaneous bone resorption is reduced in cultured calvarial bones from mice with the Chediak-Higashi syndrome, as indicated by decreased mobilization of calcium from the bones to the medium. Although bone resorption in calvaria from mice with this disease can be stimulated by PGE₂ and 1 (OH)D₃, the amounts of mineral released after stimulation is also decreased.This investigation was supported by grants from the Swedish Association against Rheumatic Diseases, from the Royal 80 Year Fund of King Gustav V, and from the Swedish Medical Research Council (project No 14X-05426).     

Effect of carbon particles on the recovery of bone marrow stem cells after irradiation in LPS-resistant C3H/HeJ mice

Effect of RES-blockade on bone marrow cells was studied serially after irradiation in LPS-resistant mice. Injection of carbon particles reduced damage and accelerated recovery of marrow hemopoietic stem cells, indicating that LPS-resistant mice can react normally to RES-blockade.     

Effect of carbon particles on the recovery of bone marrow stem cells after irradiation in LPS-resistant C3H/HeJ mice

Summary Effect of RES-blockade on bone marrow cells was studied serially after irradiation in LPS-resistant mice. Injection of carbon particles reduced damage and accelerated recovery of marrow hemopoietic stem cells, indicating that LPS-resistant mice can react normally to RES-blockade.This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.     

Small lymphocyte production and lymphoid cell proliferation in mouse bone marrow

In mice given 3H-thymidine systemically during temporary circulatory occlusion of one hind limb, comparison of the labeling of rapidly-renewing small lymphocytes in the tibial marrows demonstrated that these cells were locally produced. Labeling by 3H-thymidine infusion revealed that many marrow large lymphoid cells, presumptive small lymphocyte progenitors, had a marked proliferative activity and rapid turnover which varied according to cell size, was maximal in young mice and declined with increasing age.     

Immunological recovery of thymectomized and sham-thymectomized lethally irradiated mice reconstituted with syngeneic bone marrow cells.

Immunological functions of lethally irradiated mice reconstituted with syngeneic bone marrow cells recover after 5--6 weeks. In mice that had been thymectomized before irradiation and reconstitution, T-cell function is deficient but the B-cell function is preserved.     

Genotoxic effects of dithane M-45 on the bone marrow cells of mice in vivo

Genotoxic effects of dithane M-45 were studied on the bone marrow cells of male albino mice (Lacca strain) in vivo. Different doses (30 mg, 40 mg and 300 mg/kg b.wt) of dithane M-45 were injected intraperitoneally and their effects were investigated after time intervals of 1, 2, 5 and 10 days. The chromosomal aberrations observed in the bone marrow cells of male mice after treatment with dithane M-45 were fragments, rings, dicentric chromosomes, terminal chromatid deletions, chromatid gaps and breaks. In addition to these chromosomal aberrations, physiological effects such as uneven stretching of chromatin material, end-to-end chromosomal associations, exchange configurations, clumping, stickiness and centromeric associations were also observed.     

Genotoxic effects of dithane M-45 on the bone marrow cells of mice in vivo

Summary Genotoxic effects of dithane M-45 were studied on the bone marrow cells of male albino mice (Lacca strain) in vivo. Different doses (30 mg, 40 mg and 300 mg/kg b.wt) of dithane M-45 were injected intraperitoneally and their effects were investigated after time intervals of 1, 2, 5 and 10 days. The chromosomal aberrations observed in the bone marrow cells of male mice after treatment with dithane M-45 were fragments, rings, dicentric chromosomes, terminal chromatid deletions, chromatid gaps and breaks. In addition to these chromosomal aberrations, physiological effects such as uneven stretching of chromatin material, end-to-end chromosomal associations, exchange configurations, clumping, stickiness and centromeric associations were also observed.     

Small lymphocyte production and lymphoid cell proliferation in mouse bone marrow

Summary In mice given³H-thymidine systemically during temporary circulatory occlusion of one hind limb, comparison of the labeling of rapidly-renewing small lymphocytes in the tibial marrows demonstrated that these cells were locally produced. Labeling by³H-thymidine infusion revealed that many marrow large lymphoid cells, presumptive small lymphocyte progenitors, had a marked proliferative activity and rapid turnover which varied according to cell size, was maximal in young mice and declined with increasing age.This work was supported by a grant from the Medical Research Council of Canada. The technical assistance of Mrs E. D. Watson is acknowledged.     

Studies on experimental ancylostomiasis: transfer of acquired immunity to Ancylostoma caninum in mice through sensitized thymus and bone marrow cells.

An attempt has been made to transfer acquired immunity to Ancylostoma caninum infective larvae from infected Swiss albino female mice to nonimmune, isologous recipients of same sex, through immunized thymus and bone marrow cells. Immunized cells from donors infected with a single high dose of 1000 larvae were found to be more immunocompetent than cells from donors infected with a single, but low dose of 500 larvae.     

Radiation protection of bone marrow lymphocytes by 2-mercaptopropionylglycine (MPG)

Summary The drug, MPG, when administered before irradiation, increases the radioresistance of bone marrow lymphocytes of mice to gamma rays and helps in promoting fast recovery, especially when exposed to sublethal dose.     

New bone induction by demineralized bone matrix in immunosuppressed rats

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.     

New bone induction by demineralized bone matrix in immunosuppressed rats.

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.     

Stimulation of the growth of murine bone marrow colonies in vitro by an acute inflammatory exudate. Comparison with colony stimulating factor CSF)]

Formation of colonies from mice bone marrow progenitors of macrophages and granulocytes in methylcellulose culture was induced by an inflammatory pleural exudate obtained from mice injected with dextran. Mitogenic activity of this acute inflammatory exudate was compared with that of colony stimulating factor (CSF). It was found that colony and cluster counts, during 10 days of culture, were similar with the two types of stimulating factors. When used at the same dose, exudate was less active than CSF. It was concluded that inflammatory exudate showed an activity similar to that of CSF but contained a smaller amount of stimulating factor. Further cytochemical studies are necessary to specify whether or not the two factors induced the same type of colonies (monocytic or granulocytic).