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Human Growth Hormone Transgene Expression Increases the Biomechanical Structural Properties of Mouse Vertebrae

Steinke, Brian MD*; Patwardhan, Avinash G. PhD*†; Havey, Robert M. BS; King, Donna PhD

Basic Science

Study Design. Caudal vertebrae were obtained from male and female mice from two transgenic lines expressing an erythroid-specific human growth hormone transgene construct, and gender-matched, age-matched, non-transgenic control mice.

Objective. To characterize the effect of human growth hormone transgene expression on the biomechanical structural properties of caudal vertebrae in compression.

Summary of Background Data. An increase in trabecular and cortical bone deposition caused by erythroid-specific human growth hormone transgene expression was demonstrated previously.

Methods. Compression tests were performed on individual caudal vertebrae (Ca4, Ca5, Ca6) obtained from male and female mice from two transgenic lines (TG420 and TG450) and nontransgenic control mice. Two age groups were evaluated: 12 weeks old and 6 months old. The data were used to obtain axial stiffness, maximum load, and energy to failure.

Results. Vertebrae from male TG420 transgenic mice produced significantly larger values for maximum load, energy to failure, and axial stiffness at both 12 weeks and 6 months in comparison with their age-matched non-transgenic male controls. Vertebrae from female TG420 transgenic mice produced similar responses at 6 months. Vertebrae from male TG450 transgenic mice showed significant increases in maximum load and energy to failure at 6 months. In general, the biomechanical properties of vertebrae were significantly larger in the 6-month age group than in the 12-week age group, and this increase was significantly greater in the transgenic mice than in the gender-matched control mice during the same time span. This process was also influenced by transgenic genotype and gender.

Conclusions. Erythroid-specific production of human growth hormone in transgenic mice resulted in significant increases in biomechanical properties of their caudal vertebrae in compression. The changes in the biomechanical properties were influenced by genotype, age, and gender.

From the *Department of Orthopaedic Surgery and Rehabilitation, Loyola University Medical Center, Maywood, the †Musculoskeletal Biomechanics Laboratory, Rehabilitation Research and Development Center, Hines VA Hospital, Hines, and the ‡Department of Biochemistry and Molecular Pathology, North Eastern Ohio Universities College of Medicine, Rootstown, Ohio.

Supported by the Department of Orthopaedic Surgery and Rehabilitation, Loyola University, Medical Center, Maywood, and the Rehabilitation Research and Development Center, Hines VA Hospital, Hines, Illinois.

Acknowledgment date: June 18, 1997.

First revision date: February 3, 1998.

Acceptance date: April 20, 1998.

Device status category: 1.

Address reprint requests to: Avinash G. Patwardhan, PhD; Department of Orthopaedic Surgery and Rehabilitation; Loyola University Medical Center; 2160 S. First Avenue, Maywood, IL 60153; E-mail: apatwar@luc.edu.

© 1999 Lippincott Williams & Wilkins, Inc.