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; Susan Chubinskaya, PhD
J Bone Joint Surg Am, 2003 Aug 01;85(suppl 3):67-74
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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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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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