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Recovery of Articular Cartilage Metabolism Following Thermal Stress Is Facilitated by IGF-1 and JNK Inhibitor

Constance R. Chu, MD^*,, Lee D. Kaplan, MD, Freddie H. Fu, MD, Lawrence S. Crossett, MD and Rebecca K. Studer, PhD^,

From the Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, the Department of Orthopedic Surgery, University of Wisconsin, and the Veterans Administration Medical Center of Pittsburgh, Pittsburgh, Pennsylvania

^* Address correspondence and reprint requests to Constance R. Chu, MD, Director, Cartilage Restoration Program, University of Pittsburgh, 5200 Centre Ave, Suite 415, Pittsburgh, PA 15232.

Background: The safety of intra-articular use of thermal probes is related to whether chondrocytes can tolerate exposure to high temperatures and whether cytoprotective agents may improve chondrocyte survival after thermal injury.

Purpose: This study was conducted to characterize the metabolic responses of articular cartilage after short-term exposure to temperatures between 50°C and 60°C with and without addition of insulin-like growth factor 1 (IGF-1) and c-Jun N-terminal kinase (JNK) inhibitor.

Methods: Human articular cartilage from osteoarthritic knees was subjected to defined thermal stress.

Results: Although significant reduction of proteoglycan synthesis was observed after 5 seconds of exposure to 55°C and 60°C and after 10- to 30-second exposures to 53°C, recovery of metabolic activity levels was observed after 7 days.

Conclusion: Addition of IGF-1 and JNK inhibitor Sp600125 enabled the cartilage to maintain significantly higher levels of proteoglycan synthesis immediately after thermal stress. IGF-1 also enhanced recovery of metabolic activity after 7 days.

Clinical Significance: Results from this study indicate that there may be time and temperature parameters within which thermal chondroplasty can be safely performed. The data additionally suggest that inadvertent chondrocyte injury may be minimized through potential addition of substances like IGF-1 or JNK inhibitor.

Key Words: chondroprotection • articular cartilage • jnk-inhibitor • IGF-1 • radiofrequency probes

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