Editorial Type:
Musculoskeletal System

Age-dependent effects of systemic administration of oxytetracycline on the viscoelastic properties of rat tail tendons as a mechanistic basis for pharmacological treatment of flexural limb deformities in foals

Leslie R. Wintz Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Leslie R. Wintz in
Current site
Google Scholar
PubMed Close
 BS
,
Michael Lavagnino Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Michael Lavagnino in
Current site
Google Scholar
PubMed Close
 PhD
,
Keri L. Gardner Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Keri L. Gardner in
Current site
Google Scholar
PubMed Close
 MS
,
Aleksa M. Sedlak Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Aleksa M. Sedlak in
Current site
Google Scholar
PubMed Close
, and
Steven P. Arnoczky Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Search for other papers by Steven P. Arnoczky in
Current site
Google Scholar
PubMed Close
 DVM
DOI:
https://doi.org/10.2460/ajvr.73.12.1951
Volume/Issue:
Volume 73: Issue 12
Online Publication Date:
01 Dec 2012
Restricted access
Sign In Reprints and Permissions Purchase Article

Abstract

Objective—To describe the effect of systemically administered oxytetracycline on the viscoelastic properties of rat tail tendon fascicles (TTfs) to provide a mechanistic rationale for pharmacological treatment of flexural limb deformities in foals.

Sample—TTfs from ten 1-month-old and ten 6-month-old male Sprague-Dawley rats.

Procedures—5 rats in each age group were administered oxytetracycline (50 mg/kg, IP, q 24 h) for 4 days. The remaining 5 rats in each age group served as untreated controls. Five days after initiation of oxytetracycline treatment, TTfs were collected and their viscoelastic properties were evaluated via a stress-relaxation protocol. Maximum modulus and equilibrium modulus were compared via a 2-way ANOVA. Collagen fibril size, density, and orientation in TTfs were compared between treated and control rats.

Results—Viscoelastic properties were significantly decreased in TTfs from 1-month-old oxytetracycline-treated rats, compared with those in TTfs from 1-month-old control rats. Oxytetracycline had no effect on the viscoelastic properties of TTfs from 6-month-old rats. Collagen fibril size, density, and orientation in TTfs from 1-month-old rats did not differ between oxytetracycline-treated and control rats.

Conclusions and Clinical Relevance—Results confirmed that systemically administered oxytetracycline decreased the viscoelastic properties of TTfs from 1-month-old rats but not those of TTfs from 6-month-old rats. The decrease in viscoelastic properties associated with oxytetracycline treatment does not appear to be caused by altered collagen fibril diameter or organization. The age-dependent effect of oxytetracycline on the viscoelastic properties of tendons may be related to its effect on the maturation of the extracellular matrix of developing tendons.

Abstract

Objective—To describe the effect of systemically administered oxytetracycline on the viscoelastic properties of rat tail tendon fascicles (TTfs) to provide a mechanistic rationale for pharmacological treatment of flexural limb deformities in foals.

Sample—TTfs from ten 1-month-old and ten 6-month-old male Sprague-Dawley rats.

Procedures—5 rats in each age group were administered oxytetracycline (50 mg/kg, IP, q 24 h) for 4 days. The remaining 5 rats in each age group served as untreated controls. Five days after initiation of oxytetracycline treatment, TTfs were collected and their viscoelastic properties were evaluated via a stress-relaxation protocol. Maximum modulus and equilibrium modulus were compared via a 2-way ANOVA. Collagen fibril size, density, and orientation in TTfs were compared between treated and control rats.

Results—Viscoelastic properties were significantly decreased in TTfs from 1-month-old oxytetracycline-treated rats, compared with those in TTfs from 1-month-old control rats. Oxytetracycline had no effect on the viscoelastic properties of TTfs from 6-month-old rats. Collagen fibril size, density, and orientation in TTfs from 1-month-old rats did not differ between oxytetracycline-treated and control rats.

Conclusions and Clinical Relevance—Results confirmed that systemically administered oxytetracycline decreased the viscoelastic properties of TTfs from 1-month-old rats but not those of TTfs from 6-month-old rats. The decrease in viscoelastic properties associated with oxytetracycline treatment does not appear to be caused by altered collagen fibril diameter or organization. The age-dependent effect of oxytetracycline on the viscoelastic properties of tendons may be related to its effect on the maturation of the extracellular matrix of developing tendons.

Contributor Notes

Supported by the Wade O. Brinker Endowed Chair at Michigan State University and a National Institutes of Health T35 Summer Research Fellowship.

Address correspondence to Dr. Arnoczky (arnoczky@cvm.msu.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Dec 2012

  • 1. Auer JA. Flexural deformities. In: Auer JA, Stick JA. Equine surgery. 2nd ed. Philadelphia: WB Saunders Co, 1999;752–765.

  • 2. Auer JA. Diagnosis and treatment of flexural deformities in foals. Clin Tech Equine Pract 2006;5:282–295.

  • 3. McIlwraith CW. Diseases of joints, tendons, ligaments and related structures. In: Stashak TS, ed. Adams' lameness in horses. 4th ed. Philadelphia: Lea & Febiger, 1987;451–461.

    • Search Google Scholar
    • Export Citation

  • 4. Lokai MD. Case selection for medical management of congenital flexural deformities in foals. Equine Pract 1992;14:23–25.

  • 5. Lokai MD, Meyer RJ. Preliminary observation on oxytetracycline treatment of congenital flexural deformities in foals. Mod Vet Pract 1985;66:237–239.

    • Search Google Scholar
    • Export Citation

  • 6. Madison JB, Garber JL, Rice B, et alEffect of oxytetracycline on metacarpophalangeal and distal interphalangeal joint angles in newborn foals. J Am Vet Med Assoc 1994;204:246–249.

    • Search Google Scholar
    • Export Citation

  • 7. Arnoczky SP, Lavagnino M, Gardner KL, et alIn vitro effects of oxytetracycline on matrix metalloproteinase-1 mRNA expression and on collagen gel contraction by cultured myofibroblasts obtained from the accessory ligament of foals. Am J Vet Res 2004;65:491–496.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 8. Trumble T. Joint and skeletal disorders. In: Bernard W, Barr B, ed. Equine paediatric medicine. London: Manson, 2012;266–268.

  • 9. Hartzel DK, Arnoczky SP, Kilfoyle SJ, et alMyofibroblasts in the accessory ligament (distal check ligament) and the deep digital flexor tendon of foals. Am J Vet Res 2001;62:823–827.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 10. Jung JC, Wang PX, Zhang G, et alCollagen fibril growth during chicken tendon development: matrix metalloproteinase-2 and its activation. Cell Tissue Res 2009;336:79–89.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 11. Moore MJ, De Beaux A. A quantitative ultrastructural study of rat tail tendon from birth to maturity. J Anat 1987;153:163–169.

  • 12. Nagy Z, von Hahn HP, Verzan F. Age-related alterations in the cell nuclei and the DNA content of rat tail tendon. Gerontologia 1969;15:258–264.

  • 13. Addis PR, Lawson SEM. The role of tendon stiffness in development of equine locomotion with age. Equine Vet J 2010;42:556–560.

  • 14. Engesaeter LB, Skar AG. Effects of oxytetracycline on the mechanical properties of bone and skin in young rats. Acta Orthop Scand 1978;49:529–534.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 15. Gudmundson C. Oxytetracycline-induced fragility of growing bones. An experimental study in rats. Clin Orthop Relat Res 1971;77:284–289.

    • Search Google Scholar
    • Export Citation

  • 16. Engesaeter LB, Underdal T, Løvstad R. Effects of oxytetracycline on solubility and synthesis of collagen in young rats. Acta Orthop Scand 1980;51:43–48.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 17. Lavagnino M, Arnoczky SP. In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells. J Orthop Res 2005;23:1211–1218.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 18. Purslow PP, Wess TJ, Hukins DWL. Collagen orientation and molecular spacing during creep and stress-relaxation in soft connective tissues. J Exp Biol 1998;201:135–142.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 19. Aklonis JJ & Toblosky AV. The relationship between stress relaxation and creep. Fort Belvoir, Va: Defense Technical Information Center, 1965.

    • Search Google Scholar
    • Export Citation

  • 20. Provenzano P, Lakes R, Keenan T, et alNonlinear ligament viscoelasticity. Ann Biomed Eng 2001;29:908–914.

  • 21. Kasper CA, Clayton HM, Wright AK, et alEffects of high doses of oxytetracycline on metacarpophalangeal joint kinematics in neonatal foals. J Am Vet Med Assoc 1995;207:71–73.

    • Search Google Scholar
    • Export Citation

  • 22. Grinnell F. Fibroblasts, myofibroblasts, and wound contraction. J Cell Biol 1994;124:401–404.

  • 23. Harris AK, Stopak D, Wild P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature 1981;290:249–251.

  • 24. Stopak D, Harris AK. Connective tissue morphogenesis by fibroblast traction. Develop Biol 1982;90:383–398.

  • 25. Watanabe T, Imamura Y, Suzuki D, et alConcerted and adaptive alignment of decorin dermatan sulfate filaments in the graded organization of collagen fibrils in the equine superficial digital flexor tendon. J Anat 2012;220:156–163.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 26. Silver FH, Freeman JW, Seehra GP. Collagen self-assembly and the development of tendon mechanical properties. J Biomech 2003;36:1529–1553.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 27. Uitto VJ, Lichtenstein JR. Defects in the biochemistry of collagen in diseases of connective tissue. J Invest Dermatol 1976;66:59–79.

  • 28. Lapière CM, Nusgens B. Collagen pathology at the molecular level. In: Biochemistry of collagen. New York: Plenum Press, 1976;536.

  • 29. Barrow MV, Simpson CF, Miller EJ. Lathyrism: a review. Q Rev Biol 1974;49:101–128.

  • 30. Prockop DJ, Kivirikko KI, Tuderman L, et alThe biosynthesis of collagen and its disorders (second of two parts). N Engl J Med 1979;301:77–85.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 31. Morgan AJ, Bellamy D. Effect of a lathyrogen (aminoacetonitrile hydrochloride) on aortic physiosclerosis and skeletal mineralization in growing rats of different age. Age Aging 1976;5:155–163.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 32. Siegel RC, Pinnell SR, Martin GR. Cross-linking of collagen and elastin. Properties of lysyl oxidase. Biochemistry 1970;9:4486–4492.

  • 33. Ibsen KH, Urist MR. The biochemistry and the physiology of the tetracyclines: with special reference to mineralized tissues. Clin Orthop 1974;32:143–168.

    • Search Google Scholar
    • Export Citation

  • 34. Bailey AJ. Intermediate labile intermolecular crosslinks in collagen fibers. Biochim Biophys Acta 1968;160:447–453.

  • 35. Vogel HG. Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats. Mech Ageing Dev 1980;14:283–292.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 36. Gillis C, Pool RR, Meagher DM, et alEffect of maturation and aging on the histomorphometric and biochemical characteristics of equine superficial digital flexor tendon. Am J Vet Res 1997;58:425–430.

    • Search Google Scholar
    • Export Citation

  • 37. Patterson-Kane JC, Parry DA, Birch HL, et alAn age-related study of morphology and cross-link composition of collagen fibrils in the digital flexor tendons of young Thoroughbred horses. Connect Tissue Res 1997;36:253–260.

    • Crossref
    • Search Google Scholar
    • Export Citation

  • 38. Martin-Jimenez T, Craigmill AL, Riviere JE. Extralabel use of oxytetracycline. J Am Vet Med Assoc 1997;211:42–44.

  • 39. Porter WP, Bitar YM, Standberg JD, et alA comparison of subcutaneous and intraperitoneal oxytetracycline injection methods for control of infectious disease in the rat. Lab Anim 1985;19:3–6.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement