The short-term therapeutic effect of recombinant human bone morphogenetic protein-2 on collagenase-induced lumbar facet joint osteoarthritis in rats

Osteoarthritis Cartilage. 2007 Dec;15(12):1357-66. doi: 10.1016/j.joca.2007.04.019. Epub 2007 Jun 22.

Abstract

Objective: To determine whether an intra-articular injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) alleviates cartilage degradation in a rat model of osteoarthritis (OA) of the lumbar facet joint.

Method: The right-side facet joint OA model was created by an intra-articular injection of collagenase (type II) 2 weeks before treatment. The OA rats were divided into four groups: (1) no treatment, or intra-articular injection of either (2) saline, (3) rhBMP-2 10 ng, or (4) rhBMP-2 100 ng. The left-side facet joint served as the normal control. At 3 and 6 weeks after treatment, histological analyses were performed on the cartilage, synovium, subchondral bone and bone marrow. The cartilage and synovium were graded using a modified Mankin score and a synovium score system. Extracellular type II collagen was evaluated by immunohistochemistry.

Results: Intra-articular injection of collagenase causes OA-like changes in the facet joint. OA rats treated with rhBMP-2 at both dosages tested showed reduced severity of their cartilage lesions compared with untreated and saline-treated groups. There was a statistically significant difference in the modified Mankin score compared to the untreated and saline-treated groups. However, some rhBMP-2-treated rats at the higher dose (100 ng) showed, as a side effect, joint space obliteration caused by cartilage overgrowth. Also OA rats treated with 100 ng of rhBMP-2 displayed a significant synovium reaction at 3 weeks compared with that in other groups. Immunohistochemical analysis showed that treatment with rhBMP-2 significantly increased the content of type II collagen.

Conclusion: This study demonstrates the potential efficacy of rhBMP-2 in the alleviation of arthritic changes in a rat model of OA of the lumbar facet joint. However, treatment with a high dosage of rhBMP-2 caused adverse side effects in some animals.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology
  • Bone Morphogenetic Proteins / therapeutic use*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Matrix Metalloproteinase 8 / administration & dosage
  • Matrix Metalloproteinase 8 / adverse effects*
  • Osteoarthritis / chemically induced
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Staining and Labeling
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / therapeutic use*
  • Zygapophyseal Joint / drug effects
  • Zygapophyseal Joint / metabolism*
  • Zygapophyseal Joint / pathology*

Substances

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Collagen Type II
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Matrix Metalloproteinase 8