• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of iowaorthjLink to Publisher's site
Iowa Orthop J. 1998; 18: 19–25.
PMCID: PMC2378181

Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments.


Exogenously administered growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta) and basic fibroblast growth factor (bFGF) have been shown to affect connective tissue healing in vivo, but their intrinsic role in the healing response has not been established. In the present study, immunohistochemistry with antibodies directed against these growth factors showed that expression of PDGF, TGF-beta 1 and bFGF was increased in and around the wound site in the rabbit medial collateral ligament (MCL) seven days following surgical injury. The strong expression of PDGF correlated with the observed increased cellularity consistent with this growth factor's mitogenic and chemotactic properties. Expression of these growth factors was also increased in wounded rabbit anterior cruciate ligaments (ACL) at seven days following surgical injury, but such expression was limited to the edge of the ACL injury site and was of lesser intensity relative to the MCL. This study suggests that PDGF and TGF-beta 1, and to a lesser extent bFGF, are actively involved during the early stage of MCL healing, but have a more limited presence in the injured rabbit ACL.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ansel JC, Tiesman JP, Olerud JE, Krueger JG, Krane JF, Tara DC, Shipley GD, Gilbertson D, Usui ML, Hart CE. Human keratinocytes are a major source of cutaneous platelet-derived growth factor. J Clin Invest. 1993 Aug;92(2):671–678. [PMC free article] [PubMed]
  • Antoniades HN. Human platelet-derived growth factor (PDGF): purification of PDGF-I and PDGF-II and separation of their reduced subunits. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7314–7317. [PMC free article] [PubMed]
  • Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed]
  • Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. [PMC free article] [PubMed]
  • Baird A, Mormède P, Böhlen P. Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. Biochem Biophys Res Commun. 1985 Jan 16;126(1):358–364. [PubMed]
  • Batten ML, Hansen JC, Dahners LE. Influence of dosage and timing of application of platelet-derived growth factor on early healing of the rat medial collateral ligament. J Orthop Res. 1996 Sep;14(5):736–741. [PubMed]
  • Chen JD, Kim JP, Zhang K, Sarret Y, Wynn KC, Kramer RH, Woodley DT. Epidermal growth factor (EGF) promotes human keratinocyte locomotion on collagen by increasing the alpha 2 integrin subunit. Exp Cell Res. 1993 Dec;209(2):216–223. [PubMed]
  • Cordon-Cardo C, Vlodavsky I, Haimovitz-Friedman A, Hicklin D, Fuks Z. Expression of basic fibroblast growth factor in normal human tissues. Lab Invest. 1990 Dec;63(6):832–840. [PubMed]
  • Enenstein J, Waleh NS, Kramer RH. Basic FGF and TGF-beta differentially modulate integrin expression of human microvascular endothelial cells. Exp Cell Res. 1992 Dec;203(2):499–503. [PubMed]
  • Cromack DT, Sporn MB, Roberts AB, Merino MJ, Dart LL, Norton JA. Transforming growth factor beta levels in rat wound chambers. J Surg Res. 1987 Jun;42(6):622–628. [PubMed]
  • Gospodarowicz D, Neufeld G, Schweigerer L. Fibroblast growth factor: structural and biological properties. J Cell Physiol Suppl. 1987;Suppl 5:15–26. [PubMed]
  • Heino J, Ignotz RA, Hemler ME, Crouse C, Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed]
  • Ignotz RA, Endo T, Massagué J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem. 1987 May 15;262(14):6443–6446. [PubMed]
  • Ignotz RA, Massagué J. Cell adhesion protein receptors as targets for transforming growth factor-beta action. Cell. 1987 Oct 23;51(2):189–197. [PubMed]
  • Janat MF, Argraves WS, Liau G. Regulation of vascular smooth muscle cell integrin expression by transforming growth factor beta1 and by platelet-derived growth factor-BB. J Cell Physiol. 1992 Jun;151(3):588–595. [PubMed]
  • Joyce ME, Roberts AB, Sporn MB, Bolander ME. Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol. 1990 Jun;110(6):2195–2207. [PMC free article] [PubMed]
  • Lee J, Green MH, Amiel D. Synergistic effect of growth factors on cell outgrowth from explants of rabbit anterior cruciate and medial collateral ligaments. J Orthop Res. 1995 May;13(3):435–441. [PubMed]
  • Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest. 1989 Aug;84(2):640–646. [PMC free article] [PubMed]
  • Pierce GF, Tarpley JE, Tseng J, Bready J, Chang D, Kenney WC, Rudolph R, Robson MC, Vande Berg J, Reid P, et al. Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds. J Clin Invest. 1995 Sep;96(3):1336–1350. [PMC free article] [PubMed]
  • Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet. 1992 Jan 4;339(8784):23–25. [PubMed]
  • Schreck PJ, Kitabayashi LR, Amiel D, Akeson WH, Woods VL., Jr Integrin display increases in the wounded rabbit medial collateral ligament but not the wounded anterior cruciate ligament. J Orthop Res. 1995 Mar;13(2):174–183. [PubMed]
  • Seppä H, Grotendorst G, Seppä S, Schiffmann E, Martin GR. Platelet-derived growth factor in chemotactic for fibroblasts. J Cell Biol. 1982 Feb;92(2):584–588. [PMC free article] [PubMed]
  • Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985 Nov;43(1):277–286. [PubMed]
  • Siegbahn A, Hammacher A, Westermark B, Heldin CH. Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes. J Clin Invest. 1990 Mar;85(3):916–920. [PMC free article] [PubMed]
  • Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB, Sporn MB. Expression of transforming growth factor-beta 1 in specific cells and tissues of adult and neonatal mice. J Cell Biol. 1989 Feb;108(2):661–669. [PMC free article] [PubMed]
  • Tzeng DY, Deuel TF, Huang JS, Baehner RL. Platelet-derived growth factor promotes human peripheral monocyte activation. Blood. 1985 Jul;66(1):179–183. [PubMed]
  • Wahl SM, McCartney-Francis N, Allen JB, Dougherty EB, Dougherty SF. Macrophage production of TGF-beta and regulation by TGF-beta. Ann N Y Acad Sci. 1990;593:188–196. [PubMed]
  • Wallace CD, Amiel D. Vascular assessment of the periarticular ligaments of the rabbit knee. J Orthop Res. 1991 Nov;9(6):787–791. [PubMed]
  • Wiig ME, Amiel D, VandeBerg J, Kitabayashi L, Harwood FL, Arfors KE. The early effect of high molecular weight hyaluronan (hyaluronic acid) on anterior cruciate ligament healing: an experimental study in rabbits. J Orthop Res. 1990 May;8(3):425–434. [PubMed]
  • Wiig ME, Amiel D, Ivarsson M, Nagineni CN, Wallace CD, Arfors KE. Type I procollagen gene expression in normal and early healing of the medial collateral and anterior cruciate ligaments in rabbits: an in situ hybridization study. J Orthop Res. 1991 May;9(3):374–382. [PubMed]

Articles from The Iowa Orthopaedic Journal are provided here courtesy of The University of Iowa


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...