The Journal of Experimental Medicine
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Published online 11 November 2002 doi:10.1084/jem.20021017
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© Rockefeller University Press, 0022-1007/2002/11/1387/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 10, November 18, 2002 1387-1392

Brief Definitive Report

Concerted Action of Androgens and Mechanical Strain Shifts Bone Metabolism from High Turnover into an Osteoanabolic Mode

Ute M. Liegibel1, Ulrike Sommer1, Pascal Tomakidi2, Ulrike Hilscher1, Loes van den Heuvel1, Rainer Pirzer1, Joachim Hillmeier3, Peter Nawroth1 and Christian Kasperk1

1 Department of Medicine, Division of Osteology, Ruprecht-Karls-University, 69115 Heidelberg, Germany
2 Department of Orthodontics and Dentofacial Orthopedics, Ruprecht-Karls-University, 69120 Heidelberg, Germany
3 Department of Surgery, Ruprecht-Karls-University, 69120 Heidelberg, Germany

Address correspondence to Christian Kasperk, Dept. of Medicine, Division of Osteology, Ruprecht-Karls-University, Luisenstrasse 5, 69115 Heidelberg, Germany. Phone: 49-6221-568300; Fax: 49-6221-564359; E-mail: Christian_Kasperk{at}med.uni-heidelberg.de

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 17ß-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.

Key Words: mechanoperception • osteoblasts • fibronectin • integrins • androgens


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