title: Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode.
abstract: Adhesion of bone cells to the extracellular matrix is a crucial requirement for osteoblastic development and function. Adhesion receptors connect the extracellular matrix with the cyto-skeleton and convey matrix deformation into the cell. We tested the hypothesis that sex hormones modulate mechanoperception of human osteoblastic cells (HOB) by affecting expression of adhesion molecules like fibronectin and the fibronectin receptor. Only dihydrotestosterone (DHT), but not 17beta-estradiol, stimulated fibronectin (137%) and fibronectin receptor (252%) protein expression. The effects of deformation strain on HOB metabolism were investigated in a FlexerCell strain unit. Cyclically applied strain (2.5% elongation) increased DNA synthesis (125%) and interleukin-6 (IL-6) production (170%) without significantly affecting alkaline phosphatase (AP) activity, type I collagen (PICP), or osteoprotegerin (OPG) secretion. 10 nM DHT pretreatment abolished the mitogenic response of HOB to strain and increased AP activity (119%), PICP (163%), and OPG production (204%). In conclusion, mechanical strain stimulates bone remodeling by increasing HOB mitosis and IL-6 production. DHT enhances the osteoanabolic impact of deformation strain by increasing bone formation via increased AP activity and PICP production. At the same time, bone resorption is inhibited by decreased IL-6 and increased OPG secretion into the bone microenvironment.
authors.affiliation: Department of Medicine, Division of Osteology, Ruprecht-Karls-University, 69115 Heidelberg, Germany.
authors.forename: Ute M
authors.initials: UM
authors.lastname: Liegibel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sommer
authors.forename: Pascal
authors.initials: P
authors.lastname: Tomakidi
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hilscher
authors.forename: Loes
authors.initials: L
authors.lastname: Van Den Heuvel
authors.forename: Rainer
authors.initials: R
authors.lastname: Pirzer
authors.forename: Joachim
authors.initials: J
authors.lastname: Hillmeier
authors.forename: Peter
authors.initials: P
authors.lastname: Nawroth
authors.forename: Christian
authors.initials: C
authors.lastname: Kasperk
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001483:Base Sequence; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D017931:DNA Primers; D004261:DNA Replication; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor
chemical_list: D024042:Collagen Type I; D017931:DNA Primers; D005353:Fibronectins; D006023:Glycoproteins; D039081:Integrin alpha5beta1; D015850:Interleukin-6; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D013196:Dihydrotestosterone; D004958:Estradiol; D000469:Alkaline Phosphatase