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

T. T. Yeh, S. S. Wu, C. H. Lee, Z. H. Wen, H. S. Lee, Z. Yang, M. E. Nimni, B. Han

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1357-1366
Number of pages10
JournalOsteoarthritis and Cartilage
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 2007
Externally publishedYes

Fingerprint

Zygapophyseal Joint
Therapeutic Uses
Collagenases
Osteoarthritis
Rats
Bone
Proteins
Intra-Articular Injections
Synovial Membrane
Cartilage
Spine Osteoarthritis
Collagen Type II
Collagen
Matrix Metalloproteinase 8
Therapeutics
recombinant human bone morphogenetic protein-2
Arthritis
Joints
Bone Marrow
Immunohistochemistry

Keywords

  • BMP-2
  • Bone morphogenetic protein-2
  • Collagenase
  • Facet joint
  • Osteoarthritis
  • Zygapophysial joint

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

The short-term therapeutic effect of recombinant human bone morphogenetic protein-2 on collagenase-induced lumbar facet joint osteoarthritis in rats. / Yeh, T. T.; Wu, S. S.; Lee, C. H.; Wen, Z. H.; Lee, H. S.; Yang, Z.; Nimni, M. E.; Han, B.

In: Osteoarthritis and Cartilage, Vol. 15, No. 12, 12.2007, p. 1357-1366.

Research output: Contribution to journalArticle

Yeh, T. T. ; Wu, S. S. ; Lee, C. H. ; Wen, Z. H. ; Lee, H. S. ; Yang, Z. ; Nimni, M. E. ; Han, B. / The short-term therapeutic effect of recombinant human bone morphogenetic protein-2 on collagenase-induced lumbar facet joint osteoarthritis in rats. In: Osteoarthritis and Cartilage. 2007 ; Vol. 15, No. 12. pp. 1357-1366.
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AU - Wu, S. S.

AU - Lee, C. H.

AU - Wen, Z. H.

AU - Lee, H. S.

AU - Yang, Z.

AU - Nimni, M. E.

AU - Han, B.

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N2 - 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.

AB - 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.

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