Transplantation of Achilles tendon treated with bone morphogenetic protein 7 promotes meniscus regeneration in a rat model of massive meniscal defect

Arthritis Rheum. 2013 Nov;65(11):2876-86. doi: 10.1002/art.38099.

Abstract

Objective: This study was undertaken to examine whether bone morphogenetic protein 7 (BMP-7) induces ectopic cartilage formation in the rat tendon, and whether transplantation of tendon treated with BMP-7 promotes meniscal regeneration. Additionally, we analyzed the relative contributions of host and donor cells on the healing process after tendon transplantation in a rat model.

Methods: BMP-7 was injected in situ into the Achilles tendon of rats, and the histologic findings and gene profile were evaluated. Achilles tendon injected with 1 μg of BMP-7 was transplanted into a meniscal defect in rats. The regenerated meniscus and articular cartilage were evaluated at 4, 8, and 12 weeks. Achilles tendon from LacZ-transgenic rats was transplanted into the meniscal defect in wild-type rats, and vice versa.

Results: Injection of BMP-7 into the rat Achilles tendon induced the fibrochondrocyte differentiation of tendon cells and changed the collagen gene profile of tendon tissue to more closely approximate meniscal tissue. Transplantation of the rat Achilles tendon into a meniscal defect increased meniscal size. The rats that received the tendon treated with BMP-7 had a meniscus matrix that exhibited increased Safranin O and type II collagen staining, and showed a delay in articular cartilage degradation. Using LacZ-transgenic rats, we determined that the regeneration of the meniscus resulted from contribution from both donor and host cells.

Conclusion: Our findings indicate that BMP-7 induces ectopic cartilage formation in rat tendons. Transplantation of Achilles tendon treated with BMP-7 promotes meniscus regeneration and prevents cartilage degeneration in a rat model of massive meniscal defect. Native cells in the rat Achilles tendon contribute to meniscal regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / transplantation*
  • Animals
  • Bone Morphogenetic Protein 7 / pharmacology*
  • Cell Differentiation / physiology
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / physiology
  • Collagen / genetics
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Lac Operon
  • Male
  • Menisci, Tibial / pathology
  • Menisci, Tibial / physiology*
  • Rats
  • Rats, Inbred Lew
  • Rats, Transgenic
  • Regeneration / drug effects
  • Regeneration / physiology*
  • Synovial Membrane / cytology
  • Tibial Meniscus Injuries*

Substances

  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Collagen