International Orthopaedics

, Volume 32, Issue 3, pp 395–402

Continuous infusion of insulin-like growth factor-I into the epiphysis of the tibia

  • Aziz Abbaspour
  • Shinjiro Takata
  • Yoshito Matsui
  • Shinsuke Katoh
  • Mitsuhiko Takahashi
  • Natsuo Yasui
Original Paper

Abstract

We have developed a method to promote longitudinal bone growth at the level of a specific growth-plate (GP) in young rabbits. Insulin-like growth factor-I (IGF-I) was continuously infused by means of an osmotic pump into the bone marrow cavity of the proximal epiphysis of the tibia. Radiological measurement showed a 2-mm overgrowth of the tibia after 4 weeks of treatment, while histological analysis demonstrated a 15% increase in the thickness of the selected GP. The local infusion of IGF-I increased the numbers of both proliferative and hypertrophic chondrocytes and promoted hyperplasia of bony trabeculae within the epiphysis. The distribution of material infused locally into the epiphysis was simulated by the infusion of Indian ink using the same methodology (osmotic pump) as that for IGF-I. Most of the dye remained within the bone marrow cavity of the epiphysis, but a portion infiltrated into the GP, reaching the deep layer of the physeal chondrocytes and primary spongiosa of the metaphysis. These results suggest that the method reported here is a valid one for delivering cytokines or growth factors to the selected GP and for controlling the growth and differentiation of physeal chondrocytes.

Résumé

Nous avons mis au point une méthode pour évaluer la croissance longitudinale du cartilage de croissance chez les jeunes lapins. Nous avons utilisé pour cela une pompe osmotique avec utilisation d’un facteur de croissance (IGF1) insuline like growth factor en injection continue au niveau de la cavité médullaire à proximité de l’épiphyse du tibia. Radiologiquement, les mesures ont montré 2 mm de croissance supplémentaire sur le tibia après 4 semaines de traitement. L’analyse histologique a également montré que le cartilage s’était épaissi de 15%, le nombre de chaque type de chondrocyte étant augmenté. Par ailleurs cette perfusion d’IGF1 entraîne une hyperplasie de l’os trabéculaire au voisinage de l’épiphyse. La diffusion du produit a été visualisée à l’aide d’un marqueur à base d’encre de chine injecté en même temps dans la pompe osmotique. La plupart du liquide reste au niveau de la cavité médullaire de l’épiphyse et une partie de ce liquide s’infiltre au niveau de la plaque de croissance atteignant les couches profondes et l’os spongieux primaire de la métaphyse. Ces résultats nous permettent de penser que cette méthode est utile pour apporter des cytokines et des facteurs de croissance de façon sélective au niveau de la plaque de croissance et permet également de contrôler la croissance et la différenciation cellulaire des chondrocytes.

References

  1. 1.
    Belthur MV, Bradish CF, Gibbons PJ (2005) Late orthopaedic sequelae following meningococcal septicaemia. A multicentre study. J Bone Joint Surg Br 87:236–240PubMedCrossRefGoogle Scholar
  2. 2.
    Buckley SL, Smith G, Sponseller PD, Thompson JD, Griffin PP (1990) Open fractures of the tibia in children. J Bone Joint Surg Am 72:1462–1469PubMedGoogle Scholar
  3. 3.
    Daughaday WH, Hall K, Raben MS, Salmon WD Jr, van den Brande JL, van Wyk JJ (1972) Somatomedin: proposed designation for sulphation factor. Nature 235:107PubMedCrossRefGoogle Scholar
  4. 4.
    Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279:563–566PubMedCrossRefGoogle Scholar
  5. 5.
    Grimer RJ, Belthur M, Carter SR, Tillman RM, Cool P (2000) Extendible replacements of the proximal tibia for bone tumours. J Bone Joint Surg Br 82:255–260PubMedCrossRefGoogle Scholar
  6. 6.
    Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 113:1393–1396CrossRefGoogle Scholar
  7. 7.
    Herring JA, Tachdjian MO (2002) Tachdjian’s pediatric orthopaedics, vol. 2, 3rd edn. Saunders, Philadelphia, pp 1058–1095Google Scholar
  8. 8.
    Hunziker EB, Wagner J, Zapf J (1994) Differential effects of insulin-like growth factor I and growth hormone on developmental stages of rat growth plate chondrocytes in vivo. J Clin Invest 93:1078–1086PubMedCrossRefGoogle Scholar
  9. 9.
    Kojimoto H, Yasui N, Goto T, Matsuda S, Shimomura Y (1988) Bone lengthening in rabbits by callus distraction. The role of periosteum and endosteum. J Bone Joint Surg Br 70:543–549PubMedGoogle Scholar
  10. 10.
    Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A (2001) Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol 229:141–162PubMedCrossRefGoogle Scholar
  11. 11.
    Mohan S, Richman C, Guo R, Amaar Y, Donahue LR, Wergedal J, Baylink DJ (2003) Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms. Endocrinology 144:929–936PubMedCrossRefGoogle Scholar
  12. 12.
    Mueller K, Cortesi R, Modrowski D, Marie PJ (1994) Stimulation of trabecular bone formation by insulin-like growth factor I in adult ovariectomized rats. Am J Physiol 267:E1–E6PubMedGoogle Scholar
  13. 13.
    Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC (1998) Growth hormone and bone. Endocr Rev 19:55–79PubMedCrossRefGoogle Scholar
  14. 14.
    Ohlsson C, Nilsson A, Isaksson O, Lindahl A (1992) Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc Natl Acad Sci USA 89:9826–9830PubMedCrossRefGoogle Scholar
  15. 15.
    Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R (2002) Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut 50:642–646PubMedCrossRefGoogle Scholar
  16. 16.
    Reynolds DA (1981) Growth changes in fractured long-bones: a study of 126 children. J Bone Joint Surg Br 63:83–88PubMedGoogle Scholar
  17. 17.
    Rosen CJ (1999) Serum insulin-like growth factors and insulin-like growth factor-binding proteins: clinical implications. Clin Chem 45–48:1384–1390Google Scholar
  18. 18.
    Spencer EM, Liu CC, Si EC, Howard GA (1991) In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats. Bone 12:21–26PubMedCrossRefGoogle Scholar
  19. 19.
    Wakisaka A, Tanaka H, Barnes J, Liang CT (1998) Effect of locally infused IGF-I on femoral gene expression and bone turnover activity in old rats. J Bone Miner Res 13:13–19PubMedCrossRefGoogle Scholar
  20. 20.
    Wang J, Zhou J, Bondy CA (1999) Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. Faseb J 13–14:1985–1990Google Scholar
  21. 21.
    Woods KA, Camacho-Hubner C, Savage MO, Clark AJ (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 335:1363–1367PubMedCrossRefGoogle Scholar
  22. 22.
    Xian CJ, Howarth GS, Cool JC, Foster BK (2004) Effects of acute 5-fluorouracil chemotherapy and insulin-like growth factor-I pretreatment on growth plate cartilage and metaphyseal bone in rats. Bone 35:739–749PubMedCrossRefGoogle Scholar
  23. 23.
    Yasui N, Sato M, Ochi T, Kimura T, Kawahata H, Kitamura Y, Nomura S (1997) Three modes of ossification during distraction osteogenesis in the rat. J Bone Joint Surg Br 79:824–830PubMedCrossRefGoogle Scholar
  24. 24.
    Yasui N, Kojimoto H, Sasaki K, Kitada A, Shimizu H, Shimomura Y(1993) Factors affecting callus distraction in limb lengthening. Clin Orthop 293:55–60PubMedGoogle Scholar
  25. 25.
    Zhao G, Monier-Faugere MC, Langub MC, Geng Z, Nakayama T, Pike JW, Chernausek SD, Rosen CJ, Donahue LR, Malluche HH, Fagin JA, Clemens TL (2000) Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology 141:2674–2682PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Aziz Abbaspour
    • 1
  • Shinjiro Takata
    • 1
  • Yoshito Matsui
    • 1
  • Shinsuke Katoh
    • 1
  • Mitsuhiko Takahashi
    • 1
  • Natsuo Yasui
    • 1
  1. 1.Department of Orthopedics, Institute of Health Biosciencesthe University of Tokushima Graduate SchoolTokushimaJapan

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