Skip to main content
Top
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 5/2004

01-09-2004 | Experimental Study

Temporal expression of fibroblast growth factor receptors during primary ligament repair

Authors: Simon M. Cool, Charles P. Snyman, Victor Nurcombe, Mark Forwood

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 5/2004

Login to get access

Abstract

Following injury, it is inherently difficult to completely restore the biomechanical properties of ligaments. Relatively little is known about the cellular mechanisms controlling ligament healing. Numerous studies have implicated fibroblast growth factors (FGFs) as key molecules during the initiation of the cellular proliferation, differentiation, migration and matrix deposition that characterise wound healing. While current surgical emphasis concentrates on growth factor intervention, the role of their cognate receptors (FGFRs) has largely been overlooked. Following transection of the medial collateral ligament (MCL) in rabbits, we examined FGFR expression over a 14-day healing period. Using semi-quantitative RT-PCR, we observed a significant upregulation in FGFR2 expression after 3 days. By 7 days post injury, FGFR2 expression fell to basal levels in line with those of FGFR1 and 3, both of which remained unaffected by surgical transection. These results demonstrate a role for FGFR2 in fibroblast and endothelial cell proliferation in damaged ligament, and suggest a window for FGF therapy.
Literature
1.
go back to reference Amiel D, Nagineni CN, Choi SH et al (1995) Intrinsic properties of ACL and MCL cells and their responses to growth factors. Med Sci Sports Exerc 27:844–851PubMed Amiel D, Nagineni CN, Choi SH et al (1995) Intrinsic properties of ACL and MCL cells and their responses to growth factors. Med Sci Sports Exerc 27:844–851PubMed
2.
go back to reference Burke D, Wilkes D, Blundell TL et al (1998) Fibroblast growth factor receptors: lessons from the genes. Trends Biochem Sci 23:59–62CrossRefPubMed Burke D, Wilkes D, Blundell TL et al (1998) Fibroblast growth factor receptors: lessons from the genes. Trends Biochem Sci 23:59–62CrossRefPubMed
3.
go back to reference Chan BP, Chan KM, Maffulli N et al (1997) Effect of basic fibroblast growth factor. An in vitro study of tendon healing. Clin Orthop:239–247 Chan BP, Chan KM, Maffulli N et al (1997) Effect of basic fibroblast growth factor. An in vitro study of tendon healing. Clin Orthop:239–247
4.
go back to reference Chipperfield H, Bedi KS, Cool SM et al (2002) Heparan sulfates isolated from adult neural progenitor cells can direct phenotypic maturation. Int J Dev Biol 46:661–670PubMed Chipperfield H, Bedi KS, Cool SM et al (2002) Heparan sulfates isolated from adult neural progenitor cells can direct phenotypic maturation. Int J Dev Biol 46:661–670PubMed
5.
go back to reference Cool S, Jackson R, Pincus P et al (2002) Fibroblast growth factor receptor 4 (FGFR4) expression in newborn murine calvaria and primary osteoblast cultures. Int J Dev Biol 46:519–523PubMed Cool S, Jackson R, Pincus P et al (2002) Fibroblast growth factor receptor 4 (FGFR4) expression in newborn murine calvaria and primary osteoblast cultures. Int J Dev Biol 46:519–523PubMed
6.
go back to reference Frank C, Shrive N, Hiraoka H et al (1999) Optimisation of the biology of soft tissue repair. J Sci Med Sport 2:190–210PubMed Frank C, Shrive N, Hiraoka H et al (1999) Optimisation of the biology of soft tissue repair. J Sci Med Sport 2:190–210PubMed
7.
go back to reference Fukui N, Katsuragawa Y, Sakai H et al (1998) Effect of local application of basic fibroblast growth factor on ligament healing in rabbits. Rev Rhum Engl Ed 65:406–414PubMed Fukui N, Katsuragawa Y, Sakai H et al (1998) Effect of local application of basic fibroblast growth factor on ligament healing in rabbits. Rev Rhum Engl Ed 65:406–414PubMed
8.
go back to reference Gamble JG, Edwards CC, Max SR (1984) Enzymatic adaptation in ligaments during immobilization. Aust J Sports Med 12:221–228 Gamble JG, Edwards CC, Max SR (1984) Enzymatic adaptation in ligaments during immobilization. Aust J Sports Med 12:221–228
9.
go back to reference Hart DA, Reno C, Frank CB et al (2000) Pregnancy affects cellular activity, but not tissue mechanical properties, in the healing rabbit medial collateral ligament. J Orthop Res 18:462–471PubMed Hart DA, Reno C, Frank CB et al (2000) Pregnancy affects cellular activity, but not tissue mechanical properties, in the healing rabbit medial collateral ligament. J Orthop Res 18:462–471PubMed
10.
go back to reference Hotzel H, Demuth B, Sachse K et al (1993) Detection of mycoplasma bovis using in vitro deoxyribonucleic acid amplification. Rev Sci Tech 12:581–591PubMed Hotzel H, Demuth B, Sachse K et al (1993) Detection of mycoplasma bovis using in vitro deoxyribonucleic acid amplification. Rev Sci Tech 12:581–591PubMed
11.
go back to reference Iseki S, Wilkie AO, Morriss-Kay GM (1999) Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development 126:5611–5620PubMed Iseki S, Wilkie AO, Morriss-Kay GM (1999) Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development 126:5611–5620PubMed
12.
go back to reference Josefsson PO, Gentz CF, Johnell O et al (1987) Surgical versus nonsurgical treatment of ligamentous injuries following dislocations of the elbow joint. Clin Orthop:165–169 Josefsson PO, Gentz CF, Johnell O et al (1987) Surgical versus nonsurgical treatment of ligamentous injuries following dislocations of the elbow joint. Clin Orthop:165–169
13.
go back to reference Kastner S, Elias MC, Rivera AJ et al (2000) Gene expression patterns of the fibroblast growth factors and their receptors during myogenesis of rat satellite cells. J Histochem Cytochem 48:1079–1096PubMed Kastner S, Elias MC, Rivera AJ et al (2000) Gene expression patterns of the fibroblast growth factors and their receptors during myogenesis of rat satellite cells. J Histochem Cytochem 48:1079–1096PubMed
14.
go back to reference Kobayashi D, Kurosaka M, Yoshiya S et al (1997) Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 5:189–194CrossRefPubMed Kobayashi D, Kurosaka M, Yoshiya S et al (1997) Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 5:189–194CrossRefPubMed
15.
go back to reference Larsen E, Jensen PK, Jensen PR (1999) Long-term outcome of knee and ankle injuries in elite football. Scand J Med Sci Sports 9:285–289PubMed Larsen E, Jensen PK, Jensen PR (1999) Long-term outcome of knee and ankle injuries in elite football. Scand J Med Sci Sports 9:285–289PubMed
16.
go back to reference Lee J, Harwood FL, Akeson WH et al (1998) Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments. Iowa Orthop J 18:19–25PubMed Lee J, Harwood FL, Akeson WH et al (1998) Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments. Iowa Orthop J 18:19–25PubMed
17.
go back to reference Lind M (1996) Growth factors: possible new clinical tools. A review. Acta Orthop Scand 67:407–417PubMed Lind M (1996) Growth factors: possible new clinical tools. A review. Acta Orthop Scand 67:407–417PubMed
18.
go back to reference Lo J, Hurta RA (2002) Over-expression of K-FGF or bFGF results in altered expression of matrix metalloproteinases: correlations with malignant progression and cellular invasion. Cell Biol Int 26:319–325CrossRefPubMed Lo J, Hurta RA (2002) Over-expression of K-FGF or bFGF results in altered expression of matrix metalloproteinases: correlations with malignant progression and cellular invasion. Cell Biol Int 26:319–325CrossRefPubMed
19.
go back to reference Mancilla EE, De Luca F, Uyeda JA et al (1998) Effects of fibroblast growth factor-2 on longitudinal bone growth. Endocrinology 139:2900–2904PubMed Mancilla EE, De Luca F, Uyeda JA et al (1998) Effects of fibroblast growth factor-2 on longitudinal bone growth. Endocrinology 139:2900–2904PubMed
20.
go back to reference Marchuk L, Sciore P, Reno C et al (1998) Postmortem stability of total RNA isolated from rabbit ligament, tendon and cartilage. Biochim Biophys Acta 1379:171–177CrossRefPubMed Marchuk L, Sciore P, Reno C et al (1998) Postmortem stability of total RNA isolated from rabbit ligament, tendon and cartilage. Biochim Biophys Acta 1379:171–177CrossRefPubMed
21.
go back to reference Martin M, Lefaix J, Delanian S (2000) TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys 47:277–290CrossRefPubMed Martin M, Lefaix J, Delanian S (2000) TGF-beta1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys 47:277–290CrossRefPubMed
22.
go back to reference McNeil PL, Muthukrishnan L, Warder E et al (1989) Growth factors are released by mechanically wounded endothelial cells. J Cell Biol 109:811–822PubMed McNeil PL, Muthukrishnan L, Warder E et al (1989) Growth factors are released by mechanically wounded endothelial cells. J Cell Biol 109:811–822PubMed
23.
go back to reference Millis DL (1999) Bone- and non-bone-derived growth factors and effects on bone healing. Vet Clin North Am Small Anim Pract 29:1221–1246PubMed Millis DL (1999) Bone- and non-bone-derived growth factors and effects on bone healing. Vet Clin North Am Small Anim Pract 29:1221–1246PubMed
24.
go back to reference Murphy PG, Loitz BJ, Frank CB et al (1994) Influence of exogenous growth factors on the synthesis and secretion of collagen types I and III by explants of normal and healing rabbit ligaments. Biochem Cell Biol 72:403–409PubMed Murphy PG, Loitz BJ, Frank CB et al (1994) Influence of exogenous growth factors on the synthesis and secretion of collagen types I and III by explants of normal and healing rabbit ligaments. Biochem Cell Biol 72:403–409PubMed
25.
go back to reference Muthukrishnan L, Warder E, McNeil PL (1991) Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruptions of endothelial cells. J Cell Physiol 148:1–16PubMed Muthukrishnan L, Warder E, McNeil PL (1991) Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruptions of endothelial cells. J Cell Physiol 148:1–16PubMed
26.
27.
go back to reference Nurcombe V, Ford MD, Wildschut JA et al (1993) Developmental regulation of neural response to FGF-1 and FGF-2 by heparan sulfate proteoglycan. Science 260:103–106PubMed Nurcombe V, Ford MD, Wildschut JA et al (1993) Developmental regulation of neural response to FGF-1 and FGF-2 by heparan sulfate proteoglycan. Science 260:103–106PubMed
28.
go back to reference Nurcombe V, Smart CE, Chipperfield H et al (2000) The proliferative and migratory activities of breast cancer cells can be differentially regulated by heparan sulfates. J Biol Chem 275:30009–30018CrossRefPubMed Nurcombe V, Smart CE, Chipperfield H et al (2000) The proliferative and migratory activities of breast cancer cells can be differentially regulated by heparan sulfates. J Biol Chem 275:30009–30018CrossRefPubMed
29.
go back to reference Ornitz DM (2000) FGFs, heparan sulfate and FGFRs: complex interactions essential for development. Bioessays 22:108–112PubMed Ornitz DM (2000) FGFs, heparan sulfate and FGFRs: complex interactions essential for development. Bioessays 22:108–112PubMed
30.
go back to reference Ornitz DM, Xu J, Colvin JS et al (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271:15292–15297PubMed Ornitz DM, Xu J, Colvin JS et al (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271:15292–15297PubMed
31.
go back to reference Panossian V, Liu SH, Lane JM et al (1997) Fibroblast growth factor and epidermal growth factor receptors in ligament healing. Clin Orthop:173–180 Panossian V, Liu SH, Lane JM et al (1997) Fibroblast growth factor and epidermal growth factor receptors in ligament healing. Clin Orthop:173–180
32.
go back to reference Peters K, Ornitz D, Werner S et al (1993) Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev Biol 155:423–430CrossRefPubMed Peters K, Ornitz D, Werner S et al (1993) Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev Biol 155:423–430CrossRefPubMed
33.
go back to reference Qiao J, Bush KT, Steer DL et al (2001) Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech Dev 109:123–135CrossRefPubMed Qiao J, Bush KT, Steer DL et al (2001) Multiple fibroblast growth factors support growth of the ureteric bud but have different effects on branching morphogenesis. Mech Dev 109:123–135CrossRefPubMed
34.
go back to reference Robins AJ, Newman AP, Burks RT (1993) Postoperative return of motion in anterior cruciate ligament and medial collateral ligament injuries. The effect of medial collateral ligament rupture location. Am J Sports Med 21:20–25PubMed Robins AJ, Newman AP, Burks RT (1993) Postoperative return of motion in anterior cruciate ligament and medial collateral ligament injuries. The effect of medial collateral ligament rupture location. Am J Sports Med 21:20–25PubMed
35.
go back to reference Robinson D, Hasharoni A, Oganesian A et al (2001) Role of FGF9 and FGF receptor 3 in osteochondroma formation. Orthopedics 24:783–787PubMed Robinson D, Hasharoni A, Oganesian A et al (2001) Role of FGF9 and FGF receptor 3 in osteochondroma formation. Orthopedics 24:783–787PubMed
36.
go back to reference Root LL, Shipley GD (2000) Normal human fibroblasts produce membrane-bound and soluble isoforms of FGFR-1. Mol Cell Biol Res Commun 3:87–97PubMed Root LL, Shipley GD (2000) Normal human fibroblasts produce membrane-bound and soluble isoforms of FGFR-1. Mol Cell Biol Res Commun 3:87–97PubMed
37.
go back to reference Rundle CH, Miyakoshi N, Ramirez E et al (2002) Expression of the fibroblast growth factor receptor genes in fracture repair. Clin Orthop 403:253–263CrossRefPubMed Rundle CH, Miyakoshi N, Ramirez E et al (2002) Expression of the fibroblast growth factor receptor genes in fracture repair. Clin Orthop 403:253–263CrossRefPubMed
38.
go back to reference Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225PubMed Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225PubMed
40.
go back to reference Stauber DJ, DiGabriele AD, Hendrickson WA (2000) Structural interactions of fibroblast growth factor receptor with its ligands. Proc Natl Acad Sci 97:49–54CrossRefPubMed Stauber DJ, DiGabriele AD, Hendrickson WA (2000) Structural interactions of fibroblast growth factor receptor with its ligands. Proc Natl Acad Sci 97:49–54CrossRefPubMed
41.
go back to reference Szebenyi G, Fallon JF (1999) Fibroblast growth factors as multifunctional signaling factors. Int Rev Cytol:18545–18106 Szebenyi G, Fallon JF (1999) Fibroblast growth factors as multifunctional signaling factors. Int Rev Cytol:18545–18106
42.
go back to reference Wang Q, Green RP, Zhao G et al (2001) Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development 128:3867–3876PubMed Wang Q, Green RP, Zhao G et al (2001) Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development 128:3867–3876PubMed
43.
go back to reference Wolfman NM, Hattersley G, Cox K et al (1997) Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest 100:321–330PubMed Wolfman NM, Hattersley G, Cox K et al (1997) Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest 100:321–330PubMed
44.
go back to reference Woo SL, Smith DW, Hildebrand KA et al (1998) Engineering the healing of the rabbit medial collateral ligament. Med Biol Eng Comput 36:359–364PubMed Woo SL, Smith DW, Hildebrand KA et al (1998) Engineering the healing of the rabbit medial collateral ligament. Med Biol Eng Comput 36:359–364PubMed
45.
go back to reference Xu X, Weinstein M, Li C et al (1999) Fibroblast growth factor receptors (FGFRs) and their roles in limb development. Cell Tissue Res 296:33–43CrossRefPubMed Xu X, Weinstein M, Li C et al (1999) Fibroblast growth factor receptors (FGFRs) and their roles in limb development. Cell Tissue Res 296:33–43CrossRefPubMed
46.
go back to reference Yoshida M, Fujii K (1999) Differences in cellular properties and responses to growth factors between human ACL and MCL cells. J Orthop Sci 4:293–298CrossRefPubMed Yoshida M, Fujii K (1999) Differences in cellular properties and responses to growth factors between human ACL and MCL cells. J Orthop Sci 4:293–298CrossRefPubMed
Metadata
Title
Temporal expression of fibroblast growth factor receptors during primary ligament repair
Authors
Simon M. Cool
Charles P. Snyman
Victor Nurcombe
Mark Forwood
Publication date
01-09-2004
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 5/2004
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-003-0444-x

Other articles of this Issue 5/2004

Knee Surgery, Sports Traumatology, Arthroscopy 5/2004 Go to the issue