Abstract
Changes in structure, cellularity, hematopoietic progenitor cell and macrophage content, and osteoclast activity were investigated in the hematopoietic organs of the colony-stimulating factor 1(CSF-1)-less osteopetrotic (op/op) mouse. The data indicated that op/op mice undergo an age-related hematopoietic recovery and resolution of osteopetrosis, suggesting that the hematopoietic system has the capacity to use alternative mechanisms to compensate for the absence of an important multifunctional growth factor, CSF-1. In young animals, op/op femurs were heavily infiltrated with bone, and marrow cellularity was significantly reduced. After 6 wk of age, there was an increase in the marrow space available for hematopoiesis. The femoral cavity of op/op mice progressively enlarged, and by 22 wk of age its appearance and marrow cellularity was comparable to that of controls. The percentage of op/op mononuclear phagocytes, defined by F4/80 antigen expression, progressively increased to normal levels by 35 wk of age. There was no difference in the incidence of both primitive and mononuclear phagocyte- committed, CSF-1-responsive progenitor cells in op/op marrow, but their femoral content was significantly reduced in young mice. During the period of reduced hematopoiesis in the marrow of young op/op mice, splenic hematopoietic activity was elevated. This mutant mouse represents a system for the study of the CSF-1-independent regulatory mechanisms involved in hematopoietic regulation.
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- Arnold J., Ellis S., Radley J. M., Williams N. Compensatory mechanisms in platelet production: the response of Sl/Sld mice to 5-fluorouracil. Exp Hematol. 1991 Jan;19(1):24–28. [PubMed] [Google Scholar]
- Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
- Bartelmez S. H., Bradley T. R., Bertoncello I., Mochizuki D. Y., Tushinski R. J., Stanley E. R., Hapel A. J., Young I. G., Kriegler A. B., Hodgson G. S. Interleukin 1 plus interleukin 3 plus colony-stimulating factor 1 are essential for clonal proliferation of primitive myeloid bone marrow cells. Exp Hematol. 1989 Mar;17(3):240–245. [PubMed] [Google Scholar]
- Bertoncello I. Status of high proliferative potential colony-forming cells in the hematopoietic stem cell hierarchy. Curr Top Microbiol Immunol. 1992;177:83–94. doi: 10.1007/978-3-642-76912-2_7. [DOI] [PubMed] [Google Scholar]
- Felix R., Cecchini M. G., Fleisch H. Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology. 1990 Nov;127(5):2592–2594. doi: 10.1210/endo-127-5-2592. [DOI] [PubMed] [Google Scholar]
- Felix R., Cecchini M. G., Hofstetter W., Elford P. R., Stutzer A., Fleisch H. Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op mouse. J Bone Miner Res. 1990 Jul;5(7):781–789. doi: 10.1002/jbmr.5650050716. [DOI] [PubMed] [Google Scholar]
- Gisselbrecht S., Sola B., Fichelson S., Bordereaux D., Tambourin P., Mattei M. G., Simon D., Guenet J. L. The murine M-CSF gene is localized on chromosome 3. Blood. 1989 May 1;73(6):1742–1745. [PubMed] [Google Scholar]
- Hume D. A., Pavli P., Donahue R. E., Fidler I. J. The effect of human recombinant macrophage colony-stimulating factor (CSF-1) on the murine mononuclear phagocyte system in vivo. J Immunol. 1988 Nov 15;141(10):3405–3409. [PubMed] [Google Scholar]
- Hume D. F4/80 monoclonal antibody. J Leukoc Biol. 1992 May;51(5):517–518. [PubMed] [Google Scholar]
- Karasuyama H., Melchers F. Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur J Immunol. 1988 Jan;18(1):97–104. doi: 10.1002/eji.1830180115. [DOI] [PubMed] [Google Scholar]
- Kodama H., Yamasaki A., Nose M., Niida S., Ohgame Y., Abe M., Kumegawa M., Suda T. Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage colony-stimulating factor. J Exp Med. 1991 Jan 1;173(1):269–272. doi: 10.1084/jem.173.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marks S. C., Jr Morphological evidence of reduced bone resorption in osteopetrotic (op) mice. Am J Anat. 1982 Feb;163(2):157–167. doi: 10.1002/aja.1001630205. [DOI] [PubMed] [Google Scholar]
- Marks S. C., Jr Osteopetrosis--multiple pathways for the interception of osteoclast function. Appl Pathol. 1987;5(3):172–183. [PubMed] [Google Scholar]
- McNiece I. K., Bradley T. R., Kriegler A. B., Hodgson G. S. Subpopulations of mouse bone marrow high-proliferative-potential colony-forming cells. Exp Hematol. 1986 Oct;14(9):856–860. [PubMed] [Google Scholar]
- Naito M., Hayashi S., Yoshida H., Nishikawa S., Shultz L. D., Takahashi K. Abnormal differentiation of tissue macrophage populations in 'osteopetrosis' (op) mice defective in the production of macrophage colony-stimulating factor. Am J Pathol. 1991 Sep;139(3):657–667. [PMC free article] [PubMed] [Google Scholar]
- Pollard J. W., Hunt J. S., Wiktor-Jedrzejczak W., Stanley E. R. A pregnancy defect in the osteopetrotic (op/op) mouse demonstrates the requirement for CSF-1 in female fertility. Dev Biol. 1991 Nov;148(1):273–283. doi: 10.1016/0012-1606(91)90336-2. [DOI] [PubMed] [Google Scholar]
- Sasaki K., Matsumura G., Ito T. Crystalloid inclusion-containing macrophages in the bone marrow and red pulp of the mouse, with particular relation to age, sex and hydrocortisone administration: qualitative and quantitative electron microscopy. Arch Histol Jpn. 1983 Jun;46(3):381–391. doi: 10.1679/aohc.46.381. [DOI] [PubMed] [Google Scholar]
- Shultz L. D., Sidman C. L. Genetically determined murine models of immunodeficiency. Annu Rev Immunol. 1987;5:367–403. doi: 10.1146/annurev.iy.05.040187.002055. [DOI] [PubMed] [Google Scholar]
- Wiktor-Jedrzejczak W. W., Ahmed A., Szczylik C., Skelly R. R. Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation. J Exp Med. 1982 Nov 1;156(5):1516–1527. doi: 10.1084/jem.156.5.1516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiktor-Jedrzejczak W., Bartocci A., Ferrante A. W., Jr, Ahmed-Ansari A., Sell K. W., Pollard J. W., Stanley E. R. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4828–4832. doi: 10.1073/pnas.87.12.4828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiktor-Jedrzejczak W., Ratajczak M. Z., Ptasznik A., Sell K. W., Ahmed-Ansari A., Ostertag W. CSF-1 deficiency in the op/op mouse has differential effects on macrophage populations and differentiation stages. Exp Hematol. 1992 Sep;20(8):1004–1010. [PubMed] [Google Scholar]
- Wiktor-Jedrzejczak W., Szczylik C., Ratajczak M. Z., Ahmed A. Congenital murine osteopetrosis inherited with osteosclerotic (oc) gene: hematological characterization. Exp Hematol. 1986 Oct;14(9):819–826. [PubMed] [Google Scholar]
- Wiktor-Jedrzejczak W., Urbanowska E., Aukerman S. L., Pollard J. W., Stanley E. R., Ralph P., Ansari A. A., Sell K. W., Szperl M. Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor. Exp Hematol. 1991 Nov;19(10):1049–1054. [PubMed] [Google Scholar]
- Yoshida H., Hayashi S., Kunisada T., Ogawa M., Nishikawa S., Okamura H., Sudo T., Shultz L. D., Nishikawa S. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature. 1990 May 31;345(6274):442–444. doi: 10.1038/345442a0. [DOI] [PubMed] [Google Scholar]