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. 1982 Jan 1;92(1):227–230. doi: 10.1083/jcb.92.1.227

Recruitment of osteoclast precursors by purified bone matrix constituents

PMCID: PMC2112000  PMID: 6976967

Abstract

The osteoclast, the multinucleated giant cell of bone, is derived from circulating blood cells, most likely monocytes. Evidence has accrued that is consistent with the hypothesis that the recruitment of monocytes for osteoclast development occurs by chemotaxis. In the present study, we have examined the chemotactic response of human peripheral blood monocytes and related polymorphonuclear leucocytes to three constituents of bone matrix: peptides from Type I collagen, alpha 2-HS glycoprotein, and osteocalcin (bone gla protein). The latter two substances are among the major noncollagenous proteins of bone and are uniquely associated with calcified connective tissue. In chemotaxis assays using modified Boyden chambers, Type I collagen peptides, alpha 2HS glycoprotein, and osteocalcin evoke a dose-dependent chemotactic response in human monocytes. No chemotaxis is observed on PMNs despite their ontogenetic relationship to monocytes and their documented sensitivity to a broad range of other chemical substances. Our observations are consistent with the view that osteoclast precursors (monocytes) are mobilized by chemotaxis, and suggest that the chemoattractants responsible for this activity are derived from the bone matrix or, in the case of collagen and osteocalcin; directly from the osteoblasts which produce them.

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Selected References

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  1. Ash P., Loutit J. F., Townsend K. M. Osteoclasts derived from haematopoietic stem cells. Nature. 1980 Feb 14;283(5748):669–670. doi: 10.1038/283669a0. [DOI] [PubMed] [Google Scholar]
  2. Bonucci E. The organic-inorganic relationships in bone matrix undergoing osteoclastic resorption. Calcif Tissue Res. 1974;16(1):13–36. doi: 10.1007/BF02008210. [DOI] [PubMed] [Google Scholar]
  3. Bradley T. R., Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. doi: 10.1038/icb.1966.28. [DOI] [PubMed] [Google Scholar]
  4. Buring K. On the origin of cells in heterotopic bone formation. Clin Orthop Relat Res. 1975 Jul-Aug;(110):293–301. doi: 10.1097/00003086-197507000-00040. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Campbell P. B. An improved method for the in vitro evaluation of monocyte leukotaxis. J Lab Clin Med. 1977 Aug;90(2):381–388. [PubMed] [Google Scholar]
  7. Chambers T. J. Multinucleate giant cells. J Pathol. 1978 Nov;126(3):125–148. doi: 10.1002/path.1711260302. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. FISCHMAN D. A., HAY E. D. Origin of osteoclasts from mononuclear leucocytes in regenerating newt limbs. Anat Rec. 1962 Aug;143:329–337. doi: 10.1002/ar.1091430402. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Hall B. K. The origin and fate of osteoclasts. Anat Rec. 1975 Sep;183(1):1–11. doi: 10.1002/ar.1091830102. [DOI] [PubMed] [Google Scholar]
  12. Hauschka P. V., Lian J. B., Gallop P. M. Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3925–3929. doi: 10.1073/pnas.72.10.3925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hauschka P. V., Reid M. L. Timed appearance of a calcium-binding protein containing gamma-carboxyglutamic acid in developing chick bone. Dev Biol. 1978 Aug;65(2):426–434. doi: 10.1016/0012-1606(78)90038-6. [DOI] [PubMed] [Google Scholar]
  14. Hauschka P. V., Reid M. L. Vitamin D dependence of a calcium-binding protein containing gamma-carboxyglutamic acid in chicken bone. J Biol Chem. 1978 Dec 25;253(24):9063–9068. [PubMed] [Google Scholar]
  15. Holtrop M. E., Raisz L. G. Comparison of the effects of 1,25-dihydroxycholecalciferol, prostaglandin E2, and osteoclast-activating factor with parathyroid hormone on the ultrastructure of osteoclasts in cultured long bones of fetal rats. Calcif Tissue Int. 1979;29(3):201–205. doi: 10.1007/BF02408081. [DOI] [PubMed] [Google Scholar]
  16. Holtrop M. E., Raisz L. G., Simmons H. A. The effects of parathyroid hormone, colchicine, and calcitonin on the ultrastructure and the activity of osteoclasts in organ culture. J Cell Biol. 1974 Feb;60(2):346–355. doi: 10.1083/jcb.60.2.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. JEE W. S., NOLAN P. D. ORIGIN OF OSTEOCLASTS FROM THE FUSION OF PHAGOCYTES. Nature. 1963 Oct 19;200:225–226. doi: 10.1038/200225a0. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Kreutzer D. L., Claypool W. D., Jones M. L., Ward P. A. Isolation by hydrophobic chromatography of the chemotactic factor inactivators from human serum. Clin Immunol Immunopathol. 1979 Feb;12(2):162–176. doi: 10.1016/0090-1229(79)90005-9. [DOI] [PubMed] [Google Scholar]
  20. Miller S. C. Rapid activation of the medullary bone osteoclast cell surface by parathyroid hormone. J Cell Biol. 1978 Mar;76(3):615–618. doi: 10.1083/jcb.76.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mundy G. R., Varani J., Orr W., Gondek M. D., Ward P. A. Resorbing bone is chemotactic for monocytes. Nature. 1978 Sep 14;275(5676):132–135. doi: 10.1038/275132a0. [DOI] [PubMed] [Google Scholar]
  22. Nishimoto S. K., Price P. A. Secretion of the vitamin K-dependent protein of bone by rat osteosarcoma cells. Evidence for an intracellular precursor. J Biol Chem. 1980 Jul 25;255(14):6579–6583. [PubMed] [Google Scholar]
  23. O'Flaherty J. T., Kreutzer D. L., Ward P. A. Neutrophil aggregation and swelling induced by chemotactic agents. J Immunol. 1977 Jul;119(1):232–239. [PubMed] [Google Scholar]
  24. Postlethwaite A. E., Kang A. H. Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. J Exp Med. 1976 Jun 1;143(6):1299–1307. doi: 10.1084/jem.143.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Price P. A., Baukol S. A. 1,25-dihydroxyvitamin D3 increases serum levels of the vitamin K-dependent bone protein. Biochem Biophys Res Commun. 1981 Apr 15;99(3):928–935. doi: 10.1016/0006-291x(81)91252-3. [DOI] [PubMed] [Google Scholar]
  26. Price P. A., Otsuka A. A., Poser J. W., Kristaponis J., Raman N. Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci U S A. 1976 May;73(5):1447–1451. doi: 10.1073/pnas.73.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Price P. A., Parthemore J. G., Deftos L. J. New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest. 1980 Nov;66(5):878–883. doi: 10.1172/JCI109954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Rowe D. J., Hausmann E. Quantitative analyses of osteoclast changes in resorbing bone organ cultures. Calcif Tissue Res. 1977 Oct 20;23(3):283–289. doi: 10.1007/BF02012798. [DOI] [PubMed] [Google Scholar]
  30. Smith R. Collagen and disorders of bone. Clin Sci (Lond) 1980 Oct;59(4):215–223. doi: 10.1042/cs0590215. [DOI] [PubMed] [Google Scholar]
  31. Triffitt J. T., Owen M. E., Ashton B. A., Wilson J. M. Plasma disappearance of rabbit alpha2HS-glycoprotein and its uptake by bone tissue. Calcif Tissue Res. 1978 Dec 8;26(2):155–161. doi: 10.1007/BF02013251. [DOI] [PubMed] [Google Scholar]
  32. Triffitt J. T. Plasma proteins present in human cortical bone: enrichment of the alpha2HS-glycoprotein. Calcif Tissue Res. 1976 Nov 24;22(1):27–33. doi: 10.1007/BF02010343. [DOI] [PubMed] [Google Scholar]
  33. Zigmond S. H. Chemotaxis by polymorphonuclear leukocytes. J Cell Biol. 1978 May;77(2):269–287. doi: 10.1083/jcb.77.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]

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