title: In vivo mechanical loading modulates insulin-like growth factor binding protein-2 gene expression in rat osteocytes.
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.
authors.affiliation: Department of Endocrinology, Vrye Universiteit University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: C M A
authors.initials: CM
authors.lastname: Reijnders
authors.forename: N
authors.initials: N
authors.lastname: Bravenboer
authors.forename: P J
authors.initials: PJ
authors.lastname: Holzmann
authors.forename: F
authors.initials: F
authors.lastname: Bhoelan
authors.forename: M A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: P
authors.initials: P
authors.lastname: Lips
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013977:Tibia / Q000378:metabolism / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger