Effect of bone morphogenetic protein-12 gene transfer on posterior cruciate ligament healing in a rabbit model

Am J Sports Med. 2009 Mar;37(3):599-609. doi: 10.1177/0363546508325960. Epub 2008 Dec 4.

Abstract

Background: The posterior cruciate ligament heals to some extent after injury. However, results after conservative treatment may diminish with long-term follow-up. Bone morphogenetic protein-12 can induce formation of ligament tissues.

Hypothesis: Bone morphogenetic protein-12 gene transfer can improve the histologic and biomechanical properties of healing posterior cruciate ligaments.

Study design: Controlled laboratory study.

Methods: Bilateral posterior cruciate ligaments of 32 rabbits were injured. The cut ends in 1 limb received an injection containing 3 x 10(7) pfu recombinant bone morphogenetic protein-12 adenovirus, and the posterior cruciate ligament in the contralateral limb served as an untreated control. Eight rabbits were sacrificed at each time point of 3, 6, 12, and 26 weeks after the operation. In addition, 6 rabbits receiving a sham operation were used to obtain normal control data. The posterior cruciate ligament specimens were evaluated biomechanically and histologically.

Results: The repair tissue of the treatment group at 26 weeks was similar to the normal posterior cruciate ligament in collagen arrangement, collagen formation, and mechanical properties. At weeks 6, 12, and 26, the ultimate load, stiffness, and energy absorbed at failure of the treatment group were significantly greater than those of the untreated group.

Conclusion: Adenovirus-mediated bone morphogenetic protein-12 gene transfer in a partial posterior cruciate ligament laceration rabbit model resulted in an obvious improvement of histologic properties, tensile strength, and stiffness of the repaired ligaments, indicating improved posterior cruciate ligament healing.

Clinical relevance: Bone morphogenetic protein-12 gene transfer is a potential future strategy to improve the repair of injured posterior cruciate ligaments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / pharmacology*
  • Collagen / biosynthesis
  • Collagen / drug effects
  • Gene Transfer Techniques
  • Posterior Cruciate Ligament / injuries*
  • Rabbits
  • Tensile Strength
  • Wound Healing / drug effects*

Substances

  • Bone Morphogenetic Proteins
  • growth differentiation factor 7
  • Collagen