Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1984 May 1; 98(5): 1804–1812.
PMCID: PMC2113193

Extracellular matrix-specific induction of elastogenic differentiation and maintenance of phenotypic stability in bovine ligament fibroblasts


We studied the process of elastogenic differentiation in the bovine ligamentum nuchae to assess the mechanisms that regulate elastin gene expression during development. Undifferentiated ( nonelastin - producing) ligament cells from early gestation animals initiate elastin synthesis when grown on an extracellular matrix (ECM) substratum prepared from late gestation ligamentum nuchae. ECM from ligaments of fetal calves younger than the time when elastin production occurs spontaneously in situ (i.e., beginning the last developmental trimester at approximately 180 d of gestation) does not stimulate elastin production in undifferentiated cells. Matrix-induced differentiation requires direct cell matrix interaction, is dependent upon cell proliferation after cell-matrix contact, and can be blocked selectively by incorporation of bromodeoxyuridine into the DNA of undifferentiated cells before (but not after) contact with inducing matrix. Quantitative analysis of elastin synthesis in young cells after matrix-induced differentiation indicates that the entire cell population is competent to respond to the matrix inducer, and continued synthesis of elastin after young cells are removed from the ECM substratum indicates that the phenotypic transition to elastin synthesis is stable and heritable. Although ligament cells do not require continuous contact with ECM to express the elastin phenotype, elastin synthesis is increased substantially when elastin-producing cells are grown on ligament matrix, suggesting that elastogenic differentiation is stabilized by ECM. The matrix substratum was also found to alter the distribution of tropoelastin between the medium and matrix cell layer. When grown on tissue culture plastic, ligament cells secrete greater than 80% of newly synthesized tropoelastin into the culture medium. When cultured on ECM, however, 50-70% of the newly synthesized tropoelastin remains associated with the cell layer and is cross-linked to form insoluble elastin as shown by the incorporation of radiolabeled lysine into desmosine.

Full Text

The Full Text of this article is available as a PDF (1.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Benya PD, Padilla SR, Nimni ME. Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture. Cell. 1978 Dec;15(4):1313–1321. [PubMed]
  • Bielefeld DR, Senior RM, Yu SY. A new method for determination of elastolytic activity using (14C) labeled elastin and its application to leukocytic elastase. Biochem Biophys Res Commun. 1975 Dec 15;67(4):1553–1559. [PubMed]
  • Bieth J, Spiess B, Wermuth CG. The synthesis and analytical use of a highly sensitive and convenient substrate of elastase. Biochem Med. 1974 Dec;11(4):350–357. [PubMed]
  • Cleary EG, Sandberg LB, Jackson DS. The changes in chemical composition during development of the bovine nuchal ligament. J Cell Biol. 1967 Jun;33(3):469–479. [PMC free article] [PubMed]
  • Davidson JM, Smith K, Shibahara S, Tolstoshev P, Crystal RG. Regulation of elastin synthesis in developing sheep nuchal ligament by elastin mRNA levels. J Biol Chem. 1982 Jan 25;257(2):747–754. [PubMed]
  • Fantoni A, Lunadei M, Ullu E. Control of gene expression during the terminal differentiation of erythroid cells. Curr Top Dev Biol. 1975;9:15–38. [PubMed]
  • Folkman J, Moscona A. Role of cell shape in growth control. Nature. 1978 Jun 1;273(5661):345–349. [PubMed]
  • Fulton AB, Wan KM, Penman S. The spatial distribution of polyribosomes in 3T3 cells and the associated assembly of proteins into the skeletal framework. Cell. 1980 Jul;20(3):849–857. [PubMed]
  • Greenlee TK, Jr, Ross R, Hartman JL. The fine structure of elastic fibers. J Cell Biol. 1966 Jul;30(1):59–71. [PMC free article] [PubMed]
  • GROBSTEIN C. Inductive tissue interaction in development. Adv Cancer Res. 1956;4:187–236. [PubMed]
  • GROBSTEIN C. Some transmission characteristics of the tubule-inducing influence on mouse metanephrogenic mesenchyme. Exp Cell Res. 1957 Dec;13(3):575–587. [PubMed]
  • Hay ED. Extracellular matrix. J Cell Biol. 1981 Dec;91(3 Pt 2):205s–223s. [PMC free article] [PubMed]
  • Hill BT, Whatley S. A simple, rapid microassay for DNA. FEBS Lett. 1975 Aug 1;56(1):20–23. [PubMed]
  • Holtzer H, Weintraub H, Mayne R, Mochan B. The cell cycle, cell lineages, and cell differentiation. Curr Top Dev Biol. 1972;7:229–256. [PubMed]
  • Jones CJ, Sear CH, Grant ME. An ultrastructural study of fibroblasts derived from bovine ligamentum nuchae and their capacity for elastogenesis in culture. J Pathol. 1980 May;131(1):35–53. [PubMed]
  • Lenk R, Ransom L, Kaufmann Y, Penman S. A cytoskeletal structure with associated polyribosomes obtained from HeLa cells. Cell. 1977 Jan;10(1):67–78. [PubMed]
  • Levitt D, Dorfman A. Concepts and mechanisms of cartilage differentiation. Curr Top Dev Biol. 1974;8:103–149. [PubMed]
  • Mecham RP. Effects of extracellular matrix upon elastogenesis. Connect Tissue Res. 1981;8(3-4):241–244. [PubMed]
  • Mecham RP, Griffin GL, Madaras JG, Senior RM. Appearance of chemotactic responsiveness to elastin peptides by developing fetal bovine ligament fibroblasts parallels the onset of elastin production. J Cell Biol. 1984 May;98(5):1813–1816. [PMC free article] [PubMed]
  • Mecham RP, Lange G. Measurement by radioimmunoassay of soluble elastins from different animal species. Connect Tissue Res. 1980;7(4):247–252. [PubMed]
  • Mecham RP, Lange G. Antibodies to insoluble and solubilized elastin. Methods Enzymol. 1982;82(Pt A):744–759. [PubMed]
  • Mecham RP, Lange G. Antigenicity of elastin: characterization of major antigenic determinants on purified insoluble elastin. Biochemistry. 1982 Feb 16;21(4):669–673. [PubMed]
  • Mecham RP, Lange G, Madaras J, Starcher B. Elastin synthesis by ligamentum nuchae fibroblasts: effects of culture conditions and extracellular matrix on elastin production. J Cell Biol. 1981 Aug;90(2):332–338. [PMC free article] [PubMed]
  • Mecham RP, Madaras J, McDonald JA, Ryan U. Elastin production by cultured calf pulmonary artery endothelial cells. J Cell Physiol. 1983 Sep;116(3):282–288. [PubMed]
  • Meier L, Hay ED. Stimulation of corneal differentiation by interaction between cell surface and extracellular matrix. I. Morphometric analysis of transfilter "induction". J Cell Biol. 1975 Aug;66(2):275–291. [PMC free article] [PubMed]
  • Muir H. Structure and function of proteoglycans of cartilage and cell-matrix interactions. Soc Gen Physiol Ser. 1977;32:87–99. [PubMed]
  • Pardee AB. A restriction point for control of normal animal cell proliferation. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1286–1290. [PMC free article] [PubMed]
  • Rutter WJ, Pictet RL, Morris PW. Toward molecular mechanisms of developmental processes. Annu Rev Biochem. 1973;42:601–646. [PubMed]
  • Sage H, Mecham R, Johnson C, Bornstein P. Fetal calf ligament fibroblasts in culture secrete a low molecular weight collagen with a unique resistance to proteolytic degradation. J Cell Biol. 1983 Dec;97(6):1933–1938. [PMC free article] [PubMed]
  • Slavkin HC. Combinatorial process for extracellular matrix influences on gene expression: a hypothesis. J Craniofac Genet Dev Biol. 1982;2(2):179–189. [PubMed]
  • Sugrue SP, Hay ED. Response of basal epithelial cell surface and Cytoskeleton to solubilized extracellular matrix molecules. J Cell Biol. 1981 Oct;91(1):45–54. [PMC free article] [PubMed]
  • Thom D, Powell AJ, Lloyd CW, Rees DA. Rapid isolation of plasma membranes in high yield from cultured fibroblasts. Biochem J. 1977 Nov 15;168(2):187–194. [PMC free article] [PubMed]
  • Toole BP, Jackson G, Gross J. Hyaluronate in morphogenesis: inhibition of chondrogenesis in vitro. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1384–1386. [PMC free article] [PubMed]
  • von der Mark K, Conrad G. Cartilage cell differentiation: review. Clin Orthop Relat Res. 1979 Mar-Apr;(139):185–205. [PubMed]
  • Walther BT, Pictet RL, David JD, Rutter WJ. On the mechanism of 5-bromodeoxyuridine inhibition of exocrine pancreas differentiation. J Biol Chem. 1974 Mar 25;249(6):1953–1964. [PubMed]
  • Wirtschafter ZT, Cleary EG, Jackson DS, Sandberg LB. Histological changes during the development of the bovine nuchal ligament. J Cell Biol. 1967 Jun;33(3):481–488. [PMC free article] [PubMed]
  • Zanjani ED, Lim G, McGlave PB, Clapp JF, Mann LI, Norwood TH, Stamatoyannopoulos G. Adult haematopoietic cells transplanted to sheep fetuses continue to produce adult globins. Nature. 1982 Jan 21;295(5846):244–246. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...