Effects of growth hormone transgene expression on vertebrae in a mouse model of osteogenesis imperfecta.

Abstract

STUDY DESIGN:

A human growth hormone transgene was bred into mice of the Cola2oim (oim) lineage. Caudal (tail) vertebrae from male and female mice at early skeletal maturity and at midlife were evaluated for physical and biomechanical properties.

OBJECTIVE:

To test whether constant low-level growth hormone expression within the marrow could improve structural or material properties of caudal vertebrae in oim mice.

SUMMARY OF BACKGROUND DATA:

A spontaneous genetic defect in a type I procollagen gene created the oim mouse model for osteogenesis imperfecta. Bones of heterozygous oim mice are biomechanically inferior to wild-type controls. Bone marrow expression of human growth hormone was demonstrated previously to enhance bone deposition and structural biomechanical properties in caudal vertebrae of transgenic mice.

METHODS:

Compression tests were performed individually on three caudal vertebrae (Ca4, 5, and 6) from each mouse to determine their structural biomechanical properties. Volumetric and mineral content measurements were also made. In a subset of vertebrae, the ashing measurements were confirmed and extended by peripheral quantitative tomographic scanning, which also allowed calculation of the failure stress.

RESULTS:

Heterozygous oim mouse vertebrae had structural and material properties inferior to the wild-type controls. Growth hormone transgene expression increased the size and mineral content of the vertebrae from mutant mice, and increased biomechanical structural values for maximum load and energy to failure. Failure stress was not improved.

CONCLUSIONS:

Growth hormone stimulation of size and bone mineral content of osteogenesis imperfecta mutant mouse caudal vertebrae contributed to their improved performance in axial compression. There was no evidence for improved material properties, however.

• Authors: Donna King, Jeff Chase, Robert M Havey, Leonard Voronov, Mark Sartori, Heather A McEwen, Wesley G Beamer, Avinash G Patwardhan
• Journal: Spine (Spine (Phila Pa 1976)) Vol. 30 Issue 13 Pg. 1491-5 (Jul 01 2005) ISSN: 1528-1159 [Electronic] United States
• PMID: 15990661 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Human Growth Hormone

Topics

• Animals
• Biomechanical Phenomena
• Bone Density
• Disease Models, Animal
• Female
• Gene Expression
• Genetic Therapy (methods)
• Heterozygote
• Human Growth Hormone (genetics)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Osteogenesis Imperfecta (pathology, physiopathology, therapy)
• Spine (pathology, physiology)
• Tail