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The Journal of Bone and Joint Surgery (American) 85:67-74 (2003)
© 2003 The Journal of Bone and Joint Surgery, Inc.

Basic Science

Modulation of Endogenous Osteogenic Protein-1 (OP-1) by Interleukin-1 in Adult Human Articular Cartilage

Charis Merrihew, PhD, Stephan Soeder, MD, David C. Rueger, PhD, Klaus E. Kuettner, PhD and Susan Chubinskaya, PhD

Abstract

Background: Osteogenic protein-1 (OP-1, BMP-7) induces bone formation and cartilage growth. Since OP-1 is an anabolic factor expressed by human articular chondrocytes, we examined the response of endogenous OP-1 to interleukin-1ß (IL-1ß) in human articular cartilage.

Methods: Normal adult human articular cartilage explants were cultured for twenty-five days in the presence of medium only or were treated with a low dose (0.1 ng/mL) or high dose (1.0 ng/mL) of IL-1ß for forty-eight or ninety-six hours. Alternately, cartilage explants were cultured forty-eight hours with IL-1ß, followed by forty-eight hours in standard medium (recovery). Tissue was analyzed for OP-1 message (by means of the reverse transcriptase-polymerase chain reaction), protein (by means of enzyme-linked immunosorbent assay and Western blot analysis) and proteoglycan content. Medium was analyzed for released proteoglycans and OP-1.

Results: In the presence of medium, OP-1 maintained its steady state of mRNA and protein expression for as long as twenty-five days in culture. A low dose of IL-1ß led to some upregulation in message and a twofold (p < 0.02) increase in OP-1 protein characterized by enhanced processing and activation of OP-1. Removal of IL-1ß (recovery experiments) did not reverse its effect on OP-1 synthesis. A high dose of IL-1ß caused stronger upregulation of message and a twofold decrease in OP-1 protein content (p < 0.007) in the cartilage matrix. However, this decrease in the matrix was primarily due to a release of active OP-1 into the medium. After removal of the 1.0-ng/mL IL-1ß, the levels of OP-1 protein did not recover.

Conclusion: The results of the present study indicate that human adult chondrocytes have an ability to respond anabolically to initial or early catabolic events through an upregulation of endogenous OP-1.

Clinical Relevance: A balance between anabolism and catabolism is perturbed and not fully synchronized in the degenerative processes seen in osteoarthritis. The aim of the current study was to investigate the function of a cartilage endogenous anabolic factor, i.e., OP-1, in a model of early degeneration induced by a catabolic mediator IL-1. The findings of the present study contribute to our understanding of the mechanisms involved in articular cartilage regeneration and repair.


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