Abstract
A monocyte-derived factor with IL-1-like properties has recently been shown to cause resorption of bone in organ culture. We have investigated the action of IL-1 on disaggregated populations of osteoclasts, incubated alone or in the presence of osteoblastic cells, in an attempt to identify the target cell for IL-1 in bone, and to elucidate the mechanism by which IL-1 induces osteoclastic resorption. Osteoclasts were disaggregated from neonatal rat long bones and incubated on slices of human femoral cortical bone. Under these conditions, the majority of osteoclasts form distinctive excavations in the bone surface within 24 h, the volume of which can be quantified by computer-assisted morphometric and stereophotogrammetic techniques. IL- 1 had no effect on bone resorption by osteoclasts alone, but when incubated in the presence of calvarial cells or cloned osteosarcoma cells, it induced a 3.8 (+/- 0.38)-fold increase in osteoclastic bone resorption, with significant enhancement at concentrations of greater than or equal to 30 pg/ml. The osteoblastic populations themselves did not resorb bone. The mechanism by which osteoblastic cells stimulate osteoclasts did not appear to depend upon PG synthesis; nor could we detect a diffusible substance in the medium of stimulated cocultures. These results indicate that IL-1 stimulates bone resorption through a primary action on osteoblasts, which are induced by IL-1 to transmit a short-range signal that stimulates osteoclastic bone resorption.
Full Text
The Full Text of this article is available as a PDF (554.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bernheim H. A., Block L. H., Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979 Aug;91(2):261–270. doi: 10.7326/0003-4819-91-2-261. [DOI] [PubMed] [Google Scholar]
- Chambers T. J., Fuller K., Athanasou N. A. The effect of prostaglandins I2, E1, E2 and dibutyryl cyclic AMP on the cytoplasmic spreading of rat osteoclasts. Br J Exp Pathol. 1984 Oct;65(5):557–566. [PMC free article] [PubMed] [Google Scholar]
- Chambers T. J., Magnus C. J. Calcitonin alters behaviour of isolated osteoclasts. J Pathol. 1982 Jan;136(1):27–39. doi: 10.1002/path.1711360104. [DOI] [PubMed] [Google Scholar]
- Chambers T. J., McSheehy P. M., Thomson B. M., Fuller K. The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology. 1985 Jan;116(1):234–239. doi: 10.1210/endo-116-1-234. [DOI] [PubMed] [Google Scholar]
- Chambers T. J., Thomson B. M., Fuller K. Effect of substrate composition on bone resorption by rabbit osteoclasts. J Cell Sci. 1984 Aug;70:61–71. doi: 10.1242/jcs.70.1.61. [DOI] [PubMed] [Google Scholar]
- Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
- Duff G. W., Durum S. K. The pyrogenic and mitogenic actions of interleukin-1 are related. Nature. 1983 Aug 4;304(5925):449–451. doi: 10.1038/304449a0. [DOI] [PubMed] [Google Scholar]
- Duff G. Immune diseases. Many roles for interleukin-1. 1985 Jan 31-Feb 6Nature. 313(6001):352–353. doi: 10.1038/313352a0. [DOI] [PubMed] [Google Scholar]
- Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldberg A. L., Baracos V., Rodemann P., Waxman L., Dinarello C. Control of protein degradation in muscle by prostaglandins, Ca2+, and leukocytic pyrogen (interleukin 1). Fed Proc. 1984 Apr;43(5):1301–1306. [PubMed] [Google Scholar]
- Gowen M., Wood D. D., Ihrie E. J., McGuire M. K., Russell R. G. An interleukin 1 like factor stimulates bone resorption in vitro. Nature. 1983 Nov 24;306(5941):378–380. doi: 10.1038/306378a0. [DOI] [PubMed] [Google Scholar]
- Heath J. K., Meikle M. C., Atkinson S. J., Reynolds J. J. A factor synthesized by rabbit periosteal fibroblasts stimulates bone resorption and collagenase production by connective tissue cells in vitro. Biochim Biophys Acta. 1984 Aug 21;800(3):301–305. doi: 10.1016/0304-4165(84)90409-4. [DOI] [PubMed] [Google Scholar]
- Murphy P. A., Simon P. L., Willoughby W. F. Endogenous pyrogens made by rabbit peritoneal exudate cells are identical with lymphocyte-activating factors made by rabbit alveolar macrophages. J Immunol. 1980 May;124(5):2498–2501. [PubMed] [Google Scholar]
- Pilsworth L. M., Saklatvala J. The cartilage-resorbing protein catabolin is made by synovial fibroblasts and its production is increased by phorbol myristate acetate. Biochem J. 1983 Nov 15;216(2):481–489. doi: 10.1042/bj2160481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saklatvala J., Curry V. A., Sarsfield S. J. Purification to homogeneity of pig leucocyte catabolin, a protein that causes cartilage resorption in vitro. Biochem J. 1983 Nov 1;215(2):385–392. doi: 10.1042/bj2150385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saklatvala J., Pilsworth L. M., Sarsfield S. J., Gavrilovic J., Heath J. K. Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein. Biochem J. 1984 Dec 1;224(2):461–466. doi: 10.1042/bj2240461. [DOI] [PMC free article] [PubMed] [Google Scholar]