Abstract
The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co- cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes.
Full Text
The Full Text of this article is available as a PDF (1.9 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- Chambers T. J. Multinucleate giant cells. J Pathol. 1978 Nov;126(3):125–148. doi: 10.1002/path.1711260302. [DOI] [PubMed] [Google Scholar]
- Cline M. J., Moore M. A. Embryonic origin of the mouse macrophage. Blood. 1972 Jun;39(6):842–849. [PubMed] [Google Scholar]
- Coccia P. F., Krivit W., Cervenka J., Clawson C., Kersey J. H., Kim T. H., Nesbit M. E., Ramsay N. K., Warkentin P. I., Teitelbaum S. L. Successful bone-marrow transplantation for infantile malignant osteopetrosis. N Engl J Med. 1980 Mar 27;302(13):701–708. doi: 10.1056/NEJM198003273021301. [DOI] [PubMed] [Google Scholar]
- Goud T. J., Schotte C., van Furth R. Identification and characterization of the monoblast in mononuclear phagocyte colonies grown in vitro. J Exp Med. 1975 Nov 1;142(5):1180–1199. doi: 10.1084/jem.142.5.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Göthlin G., Ericsson J. L. The osteoclast: review of ultrastructure, origin, and structure-function relationship. Clin Orthop Relat Res. 1976 Oct;(120):201–231. [PubMed] [Google Scholar]
- Jotereau F. V., Le Douarin N. M. The development relationship between osteocytes and osteoclasts: a study using the quail-chick nuclear marker in endochondral ossification. Dev Biol. 1978 Apr;63(2):253–265. doi: 10.1016/0012-1606(78)90132-x. [DOI] [PubMed] [Google Scholar]
- Kahn A. J., Simmons D. J. Investigation of cell lineage in bone using a chimaera of chick and quial embryonic tissue. Nature. 1975 Nov 27;258(5533):325–327. doi: 10.1038/258325a0. [DOI] [PubMed] [Google Scholar]
- Kahn A. J., Stewart C. C., Teitelbaum S. L. Contact-mediated bone resorption by human monocytes in vitro. Science. 1978 Mar 3;199(4332):988–990. doi: 10.1126/science.622581. [DOI] [PubMed] [Google Scholar]
- Loutit J. F., Sansom J. M. Osteopetrosis of microphthalmic mice -- a defect of the hematopoietic stem cell.? Calcif Tissue Res. 1976 Jun 14;20(3):251–259. doi: 10.1007/BF02546413. [DOI] [PubMed] [Google Scholar]
- Mundy C. R., Altman A. J., Gondek M. D., Bandelin J. G. Direct resorption of bone by human monocytes. Science. 1977 Jun 3;196(4294):1109–1111. doi: 10.1126/science.16343. [DOI] [PubMed] [Google Scholar]
- Raisz L. G., Niemann I. Effect of phosphate, calcium and magnesium on bone resorption and hormonal responses in tissue culture. Endocrinology. 1969 Sep;85(3):446–452. doi: 10.1210/endo-85-3-446. [DOI] [PubMed] [Google Scholar]
- Rifkin B. R., Baker R. L., Coleman S. J. An ultrastructural study of macrophage-mediated resorption of calcified tissue. Cell Tissue Res. 1979 Oct 2;202(1):125–132. doi: 10.1007/BF00239225. [DOI] [PubMed] [Google Scholar]
- Rodan G. A., Martin T. J. Role of osteoblasts in hormonal control of bone resorption--a hypothesis. Calcif Tissue Int. 1981;33(4):349–351. doi: 10.1007/BF02409454. [DOI] [PubMed] [Google Scholar]
- Scherft J. P. The lamina limitans of the organic matrix of calcified cartilage and bone. J Ultrastruct Res. 1972 Feb;38(3):318–331. doi: 10.1016/s0022-5320(72)90008-1. [DOI] [PubMed] [Google Scholar]
- Sutton J. S., Weiss L. Transformation of monocytes in tissue culture into macrophages, epithelioid cells, and multinucleated giant cells. An electron microscope study. J Cell Biol. 1966 Feb;28(2):303–332. doi: 10.1083/jcb.28.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker D. G. Control of bone resorption by hematopoietic tissue. The induction and reversal of congenital osteopetrosis in mice through use of bone marrow and splenic transplants. J Exp Med. 1975 Sep 1;142(3):651–663. doi: 10.1084/jem.142.3.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Meer J. W., van de Gevel J. S., Elzenga-Claassen I., van Furth R. Suspension cultures of mononuclear phagocytes in the teflon culture bag. Cell Immunol. 1979 Jan;42(1):208–212. doi: 10.1016/0008-8749(79)90236-3. [DOI] [PubMed] [Google Scholar]