Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia

Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia

Mechanical loading plays an essential role in maintaining skeletal integrity. Mechanical stimulation leads to increased bone formation. However, the cellular and molecular mechanisms that are involved in the translation of mechanical stimuli into bone formation, are not completely understood. Growth...

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Bibliographic Details
Published in:Journal of endocrinology Vol. 192; no. 1; pp. 131 - 140
Main Authors: Reijnders, Christianne M A, Bravenboer, Nathalie, Tromp, Annechien M, Blankenstein, Marinus A, Lips, Paul
Format: Journal Article
Language:English
Published: Colchester BioScientifica 01-01-2007
Portland Press
Subjects:
Animals
Biological and medical sciences
Biomechanical Phenomena
Female
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene Expression Regulation - physiology
In Situ Hybridization - methods
Insulin-Like Growth Factor I - analysis
Insulin-Like Growth Factor I - genetics
Molecular and cellular biology
Molecular genetics
Osteocytes - metabolism
Osteogenesis
Radioimmunoassay
Random Allocation
Rats
Rats, Wistar
Regular papers
RNA, Messenger - analysis
Tibia - metabolism
Weight-Bearing - physiology
In vivo
Vertebrata
Mammalia
Rat
Animal
Rodentia
Skeleton
Gene expression
Insulin like growth factor 1
Osteocyte
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Summary:Mechanical loading plays an essential role in maintaining skeletal integrity. Mechanical stimulation leads to increased bone formation. However, the cellular and molecular mechanisms that are involved in the translation of mechanical stimuli into bone formation, are not completely understood. Growth factors and osteocytes, which act as mechanosensors, play a key role during the bone formation after mechanical stimulation. The aim of this study was to characterize the role of IGF-I in the translation of mechanical stimuli into bone formation locally in rat tibiae. Fifteen female Wistar rats were randomly assigned to three groups (n = 5): load, sham-loaded, and control. The four-point bending model of Forwood and Turner was used to induce a single period of mechanical loading on the tibia shaft. The effects of mechanical loading on IGF-I mRNA expression were determined with non-radioactive in situ hybridization on decalcified tibiae sections, 6 h after the loading session. Endogenous IGF-I mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and sub-endocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGF-I mRNA. In the growth plate, IGF-I mRNA was located in proliferative and hypertrophic chondrocytes. Mechanical loading did not affect the IGF-I mRNA expression in osteoblasts, bone marrow cells, and chondrocytes, but the osteocytes at the endosteal side of the shaft showed a twofold increase of IGF-I mRNA expression. The proportion of IGF-I mRNA positive osteocytes in loaded tibiae was 29.3 ± 12.9% (mean ± s.d.; n = 5), whereas sham-loaded and contra-lateral control tibiae exhibited 16.7 ± 4.4% (n = 5) and 14.7 ± 4.2% (n = 10) respectively (P < 0.05). Lamellar bone formation after a single mechanical loading session was observed at the endosteal side of the shaft. In conclusion, a single loading session results in a twofold up-regulation of IGF-I mRNA synthesis in osteocytes which are present in multiple layers extending into the cortical bone of mechanically stimulated tibia shaft 6 h after loading. This supports the hypothesis that IGF-I, which is located in osteocytes, is involved in the translation of mechanical stimuli into bone formation.
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ISSN:0022-0795
1479-6805
DOI:10.1677/joe.1.06880