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. 1976 Jun 1;69(3):557–572. doi: 10.1083/jcb.69.3.557

Collagenous bone matrix-induced endochondral ossification hemopoiesis

PMCID: PMC2109708  PMID: 1270511

Abstract

Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone marrow develops within the newly formed ossicle. On day 1, the implanted matrix was a discrete conglomerate with fibrin clot and polymorphonuclear leukocytes. By day 3, the leukocytes disappeared, and this event was followed by migration and close apposition of fibroblast cell surface to the collagenous matrix. This initial matrix-membrane interaction culminated in differentiation of fibroblasts to chondroblasts and osteoblasts. The calcification of the hypertrophied chondrocytes and new bone formation were correlated with increased alkaline phosphatase activity and 45Ca incorporation. The ingrowth of capillaries on day 9 resulted in chondrolysis and osteogenesis. Further remodelling of bony trabeculae by osteoclasts resulted in an ossicle of cancellous bone. This was followed by emergence of extravascular islands of hemocytoblasts and their differentiation into functional bone marrow with erythropoietic and granulopoietic elements and megakaryocytes in the ossicle. The onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme. These findings imply a role for extracellular collagenous matrix in cell differentiation.

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Selected References

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  1. Anderson H. C. Vesicles associated with calcification in the matrix of epiphyseal cartilage. J Cell Biol. 1969 Apr;41(1):59–72. doi: 10.1083/jcb.41.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonucci E. The locus of initial calcification in cartilage and bone. Clin Orthop Relat Res. 1971;78:108–139. doi: 10.1097/00003086-197107000-00010. [DOI] [PubMed] [Google Scholar]
  3. Crissman R. S., Low F. N. A study of fine structural changes in the cartilage-to-bone transition within the developing chick vertebra. Am J Anat. 1974 Aug;140(4):451–469. doi: 10.1002/aja.1001400402. [DOI] [PubMed] [Google Scholar]
  4. GODMAN G. C., PORTER K. R. Chondrogenesis, studied with the electron microscope. J Biophys Biochem Cytol. 1960 Dec;8:719–760. doi: 10.1083/jcb.8.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GONZALES F., KARNOVSKY M. J. Electron microscopy of osteoclasts in healing fracturees of rat bone. J Biophys Biochem Cytol. 1961 Feb;9:299–316. doi: 10.1083/jcb.9.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  7. HUGGINS C., MORII S. Selective adrenal necrosis and apoplexy induced by 7, 12-dimethylbenz(a)anthracene. J Exp Med. 1961 Nov 1;114:741–760. doi: 10.1084/jem.114.5.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. MOLONEY W. C. Leukocyte alkaline phosphatase activity in the rat. Ann N Y Acad Sci. 1958 Oct 13;75(1):31–36. doi: 10.1111/j.1749-6632.1958.tb36848.x. [DOI] [PubMed] [Google Scholar]
  10. Martland M., Hansman F. S., Robison R. The Phosphoric-Esterase of Blood. Biochem J. 1924;18(5):1152–1160. doi: 10.1042/bj0181152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Matukas V. J., Krikos G. A. Evidence for changes in protein polysaccharide associated with the onset of calcification in cartilage. J Cell Biol. 1968 Oct;39(1):43–48. doi: 10.1083/jcb.39.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. PEASE D. C. An electron microscopic study of red bone marrow. Blood. 1956 Jun;11(6):501–526. [PubMed] [Google Scholar]
  13. PORTER K. R., HAWN C. V. Z. Sequences in the formation of clots from purified bovine fibrinogen and thrombin; a study with the electron microscope. J Exp Med. 1949 Sep;90(3):225–232. doi: 10.1084/jem.90.3.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reddi A. H., Huggins C. B. Cyclic electrochemical inactivation and restoration of competence of bone matrix to transform fibroblasts. Proc Natl Acad Sci U S A. 1974 May;71(5):1648–1652. doi: 10.1073/pnas.71.5.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reddi A. H., Huggins C. B. Formation of bone marrow in fibroblast-transformation ossicles. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2212–2216. doi: 10.1073/pnas.72.6.2212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reddi A. H., Huggins C. B. Influence of geometry of transplanted tooth and bone on transformation of fibroblasts. Proc Soc Exp Biol Med. 1973 Jul;143(3):634–637. doi: 10.3181/00379727-143-37381. [DOI] [PubMed] [Google Scholar]
  17. Reddi A. H., Huggins C. Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1601–1605. doi: 10.1073/pnas.69.6.1601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reddi A. H., Huggins C. Lactic-malic dehydrogenase quotients during transformation of fibroblasts into cartilage and bone. Proc Soc Exp Biol Med. 1971 May;137(1):127–129. doi: 10.3181/00379727-137-35527. [DOI] [PubMed] [Google Scholar]
  19. Robison R. The Possible Significance of Hexosephosphoric Esters in Ossification. Biochem J. 1923;17(2):286–293. doi: 10.1042/bj0170286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. SCOTT B. L., PEASE D. C. Electron microscopy of the epiphyseal apparatus. Anat Rec. 1956 Dec;126(4):465–495. doi: 10.1002/ar.1091260405. [DOI] [PubMed] [Google Scholar]
  21. Schenk R. K., Spiro D., Wiener J. Cartilage resorption in the tibial epiphyseal plate of growing rats. J Cell Biol. 1967 Jul;34(1):275–291. doi: 10.1083/jcb.34.1.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thyberg J. Electron microscopic studies on the initial phases of calcification in guinea pig epiphyseal cartilage. J Ultrastruct Res. 1974 Feb;46(2):206–218. doi: 10.1016/s0022-5320(74)80056-0. [DOI] [PubMed] [Google Scholar]
  23. Urist M. R. Bone: formation by autoinduction. Science. 1965 Nov 12;150(3698):893–899. doi: 10.1126/science.150.3698.893. [DOI] [PubMed] [Google Scholar]
  24. Urist M. R. The substratum for bone morphogenesis. Symp Soc Dev Biol. 1970;29:125–163. [PubMed] [Google Scholar]

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