Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Archives of Orthopaedic and Trauma Surgery
Published in: Archives of Orthopaedic and Trauma Surgery 9/2004

01-11-2004 | Original Article

The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture healing: an immunohistochemical study in rats

Authors: Wolf Petersen, Britt Wildemann, Thomas Pufe, Michael Raschke, Gerhard Schmidmaier

Published in: Archives of Orthopaedic and Trauma Surgery | Issue 9/2004

Login to get access

Abstract

Introduction

Formation of new blood vessels is essential for the process of fracture healing.

Materials and methods

We investigated the expression of the angiogenic factor pleiotrophin/HB-GAM in a closed fracture model in rats by immunohistochemical methods.

Results

Histologically, 5 days after fracture the callus was predominantly composed of fibrous tissue. On day 10 a prominent chondral callus connected both ends of the fractured tibia. There was a continuous transition from the chondral callus to the newly formed bone adjacent to the corticalis of the tibia. On day 15 the amount of woven bone had increased, and in 3 of 5 animals the proximal and distal tibiae were connected by a bridge of woven bone. Pleiotrophin could be immunostained in fibroblasts and endothelial cells of the fibrous tissue between the fractured tibia ends. The chondral callus remained largely pleiotrophin-negative. Only single chondrocytes adjacent to the newly formed bone were pleiotrophin-positive. On days 10 and 15 strong immunoreactivity for pleiotrophin in the well vascularized, newly formed, woven bone was detectable. Osteoblasts, endothelial cells and fibroblasts were strongly pleiotrophin-positive.

Conclusions

These results show the presence of the angiogenic peptide pleiotrophin during fracture healing.
Literature
1.
Bonnarens F, Einhorn TA (1984) Production of a standard closed fracture in laboratory animal bone. J Orthop Res 2:97–101PubMed
2.
Brookes M, Revell WJ (1998) Blood supply of bone. Springer, Berlin Heidelberg New York
3.
Callard R, Gearing A (1994) The cytokine facts book. Academic Press, London
4.
Dreyfuß J, Brunet-de Carvalho N, Duprez D, Vigny M (1998) HB-GAM/pleiotrophin: localization of mRNA and protein in the chicken developing leg. Int J Dev Biol 42: 189–198PubMed
5.
Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop 355: 7–21
6.
Fang W, Hartmann N, Chow DT, Riegel AT, Wellstein A (1992) Pleiotrophin stimulates fibroblasts and endothelial and epithelial cells and is expressed in human cancer. J Biol Chem 267: 25889–25897PubMed
7.
Ferrara N (1999) Molecular and biological properties of vascular endothelial growth factor. J Mol Med 77:527–543PubMed
8.
Frost HM (1989) The biology of fracture healing. An overview for clinicians. Part I. Clin Orthop 248:283–293PubMed
9.
Gerber HP, Vu TH, Ryan AM, Kolwalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628PubMed
10.
Hsiu-Jeng Y, Yong YH, Jan X, Chung Y, Deul TF (1998) Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury. J Neurosci 18:3699–3707PubMed
11.
Kurtz A, Schulte AM, Wellstein A (1995) Pleiotrophin and midkine in normal development and tumor biology.Crit Rev Oncog 6:151–177PubMed
12.
Li YS, Gurrieri M, Deul TF (1990) Pleiotrophin gene expression is highly restricted and is regulated by plateled-derived growth factor. Biochem Biophys Res Comm 184:427–432
13.
Misiadis TA, Salmivirta M, Muramatsu T, Muramatsu H, Rauvala H, Lehtonen E, Jalkanen M, Thesleff I (1992) Expression of the heparin binding cytokines, midkine (MK) and HB-GAM (pleitrophin), is associated with epithelial-mesenchymal interactions during fetal development and organogenesis: Development 121:37–51
14.
Neame PJ, Young CN, Brock CW, Treep JT, Ganey TM, Sasse J, Rosenberg LC (1993) Pleiotrophin is an abundant protein in dissociative extracts of bovine fetal epiphyseal cartilage and nasal cartilage from newborns. J Orthop Res 11:479–491PubMed
15.
Petersen W, Rafii M (2001) Immunolocalisation of pleiotrophin on the growth plate of mice. Arch Orthop Trauma Surg 121:354CrossRef
16.
Relf M, LeJeune S, Scott PA, Fox S, Smith K, Leek R, Moghaddam A, Withehouse R, Bicknell R, Harris AL (1997) Expression of the angiogenic factors vascular endothelial growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet derived endothelial growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57:963–969PubMed
17.
Schmidmaier G, Wildemann B, Cromme F, Kandziora F, Haas NP, Raschke M (2002) Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats. Bone 30:816–822CrossRefPubMed
18.
Shinji I, Kaksonen M, Raulo E, Kinnunen T, Fages C, Meng X, Lasko M, Rauvala H (1998) Osteoblast recruitment and bone formation enhanced by cell matrix-associated heparin-binding growth associated molecule (HB-GAM). J Cell Biol 143:1113–1128CrossRefPubMed
19.
Tezuka KS, Takeshita Y, Hakeda M, Kumagawa R, Kikuno R, Hashimoto-Gotoh (1990) Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissue. Biochem Biophys Res Comm 173:246–251PubMed
20.
Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ (1992) Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues. Anat Embryol 186:387–406PubMed
21.
Zhang N, Deul TF (1999) Pleiotrophin and midkine, a family of mitogenic and angiogenic heparin-binding growth and differentiation factors. Curr Opin Hematol 6:223–234CrossRef
Metadata
Title
The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture healing: an immunohistochemical study in rats
Authors
Wolf Petersen
Britt Wildemann
Thomas Pufe
Michael Raschke
Gerhard Schmidmaier
Publication date
01-11-2004
Publisher
Springer-Verlag
Published in
Archives of Orthopaedic and Trauma Surgery / Issue 9/2004
Print ISSN: 0936-8051
Electronic ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-003-0582-0

Other articles of this Issue 9/2004

Archives of Orthopaedic and Trauma Surgery 9/2004 Go to the issue

Original Article

Biomechanical and histologic comparison of Achilles tendon ruptures reinforced with intratendinous and peritendinous plantaris tendon grafts in rabbits: an experimental study

Original Article

Natural history and pathogenesis of the patella clunk syndrome

Original Article

Soft-tissue graft fixation in posterior cruciate ligament reconstruction: evaluation of the effect of tibial insertion site on joint kinematics and in situ forces using a robotic/UFS testing system

Original Article

Effect of high tibial flexion osteotomy on cartilage pressure and joint kinematics: a biomechanical study in human cadaveric knees

Original Article

Anatomic basis for a minimally invasive approach to the subtalar joint

Case Report

Mechanism of combined injuries of the posterior cruciate ligament and the posterolateral ligament while wake boarding