Reijnders C M A, Bravenboer N, Holzmann P J, Bhoelan F, Blankenstein M A, Lips P
Department of Endocrinology, Vrye Universiteit University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Calcif Tissue Int. 2007 Feb;80(2):137-43. doi: 10.1007/s00223-006-0077-4. Epub 2007 Feb 3.
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.
机械刺激对于维持骨骼完整性至关重要。机械敏感性骨细胞在成骨反应过程中很重要。生长激素 - 胰岛素样生长因子(GH - IGF)轴在骨形成和重塑的调节中起关键作用。胰岛素样生长因子结合蛋白(IGFBPs)能够调节IGF活性。本研究的目的是在大鼠胫骨中局部表征IGFBP - 2在将机械刺激转化为骨形成中的作用。将雌性Wistar大鼠分为三组(n = 5):加载组、假手术组和对照组。采用四点弯曲模型对胫骨干施加单个周期的机械负荷。在脱钙胫骨切片上用非放射性原位杂交法测定刺激后6小时对IGFBP - 2 mRNA表达的影响。内源性IGFBP - 2 mRNA在小梁和皮质成骨细胞、一些小梁和皮质下骨细胞、血管的皮质内内皮细胞以及骨膜中表达。巨核细胞、巨噬细胞和髓细胞也表达IGFBP - 2 mRNA。加载和假加载对成骨细胞、骨髓细胞和软骨细胞中的IGFBP - 2 mRNA表达没有影响。在加载(1.68倍)和假加载(1.35倍)的胫骨干皮质内侧显示IGFBP - 2 mRNA阳性骨细胞增加。总之,在单次加载后6小时,挤压和弯曲的胫骨中,干骺端内侧和内板中表达IGFBP - 2 mRNA的骨细胞数量增加。机械刺激调节皮质内骨细胞中IGFBP - 2 mRNA的表达。我们认为IGFBP - 2在板层骨形成过程中起作用。