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. 2007 Feb;80(2):137-43.
doi: 10.1007/s00223-006-0077-4. Epub 2007 Feb 3.

In vivo mechanical loading modulates insulin-like growth factor binding protein-2 gene expression in rat osteocytes

C M A Reijnders  1 , N Bravenboer, P J Holzmann, F Bhoelan, M A Blankenstein, P Lips
Affiliations

In vivo mechanical loading modulates insulin-like growth factor binding protein-2 gene expression in rat osteocytes

C M A Reijnders et al. Calcif Tissue Int. 2007 Feb.

Abstract

Mechanical stimulation is essential for maintaining skeletal integrity. Mechanosensitive osteocytes are important during the osteogenic response. The growth hormone-insulin-like growth factor (GH-IGF) axis plays a key role during regulation of bone formation and remodeling. Insulin-like growth factor binding proteins (IGFBPs) are able to modulate IGF activity. The aim of this study was to characterize the role of IGFBP-2 in the translation of mechanical stimuli into bone formation locally in rat tibiae. Female Wistar rats were assigned to three groups (n = 5): load, sham, and control. The four-point bending model was used to induce a single period of mechanical loading on the tibial shaft. The effect on IGFBP-2 mRNA expression 6 hours after stimulation was determined with nonradioactive in situ hybridization on decalcified tibial sections. Endogenous IGFBP-2 mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and subendocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGFBP-2 mRNA. Loading and sham loading did not affect IGFBP-2 mRNA expression in osteoblasts, bone marrow cells, and chondrocytes. An increase of IGFBP-2 mRNA-positive osteocytes was shown in loaded (1.68-fold) and sham-loaded (1.35-fold) endocortical tibial shaft. In conclusion, 6 hours after a single loading session, the number of IGFBP-2 mRNA-expressing osteocytes at the endosteal side of the shaft and inner lamellae was increased in squeezed and bended tibiae. Mechanical stimulation modulates IGFBP-2 mRNA expression in endocortical osteocytes. We suggest that IGFBP-2 plays a role in the lamellar bone formation process.

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Figures

Fig. 1
Fig. 1
Expression of IGFBP-2 mRNA in rat brain sections (A, B) and in longitudinal control (C-G), sham-loaded (H), and loaded (J) tibial sections of 12-week-old female Wistar rats. The RNA signal is shown as a blue precipitate. The sections were counterstained with nuclear fast red and visualized under brightfield illumination. The scale bars represent 100 μm (A, B), 50 μm (D, E, G-J), and 100 μm (C, F). (A) IGFBP-2 mRNA expression within the choroid plexus of a control rat brain; red blood cells are negative and do not express IGFBP-2 mRNA. (B) Hybridization with representative IGFBP-2 sense probe showed no signal in the choroid plexus. (C) IGFBP-2 mRNA expression in the chondrocytes of the growth plate and osteoblasts of the trabecular bone. (D) IGFBP-2 mRNA expression in the periosteum of a control tibia; the osteocytes in the periosteal side of the shaft do not express IGFBP-2 mRNA. (E) IGFBP-2 mRNA expression in osteoblasts situated against the surface of normal trabecular bone and IGFBP-2-positive bone marrow cells. (F) Hybridization with a corresponding IGFBP-2 sense probe showed no signal in the osteoblasts, chondrocytes, and bone marrow cells of a control tibia. (G) IGFBP-2 mRNA expression within the superficial endocortical osteocytes (indicated by arrowheads), osteoblasts, and intracortical endothelial cells of a blood vessel of a control tibia. (H) IGFBP-2 mRNA expression in the endocortical osteocytes within multiple layers (indicated by arrowheads) and osteoblasts of a sham-loaded tibia. (J) IGFBP-2 mRNA expression in the endocortical osteocytes within multiple layers (indicated by arrowheads) and osteoblasts of a loaded tibia.
Fig. 2
Fig. 2
Influence of mechanical loading on IGFBP-2 mRNA expression in osteocytes at the endosteal side of the shaft within individual rat tibiae. Values are expressed as (A) percentage IGFBP-2 mRNA-positive osteocytes in control versus contralateral loaded tibiae (**P = 0.001, n = 5) and (B) percentage IGFBP-2 mRNA positive osteocytes in control versus contralateral sham-loaded tibiae (*P = 0.031, n = 5). No statistical differences of IGFBP-2 mRNA-positive osteocytes were observed between the control load and control sham groups (P = 0.475) or between the load and sham groups (P = 0.468). The lines connect the left and right tibiae of the same rat. The mean values of each group are represented by a bar.
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