tgf-β1 as possible link between loss of bone mineral density and chronic inflammationtgf-β1尽可能联系骨密度和慢性炎症.pdfVIP

TGF-b1 As Possible Link between Loss of Bone Mineral Density and Chronic Inflammation 1 1 1 1 1 2 Sabrina Ehnert *, Johannes Baur , Andreas Schmitt , Markus Neumaier , Martin Lucke , Steven Dooley , 1 3 ¨ 1 1 Helen Vester , Britt Wildemann , Ulrich Stockle , Andreas K. Nussler ¨ ¨ ¨ 1 Department of Traumatology, MRI, Technische Universitat Munchen, Munchen, Germany, 2 Department of Medicine II, University Hospital Mannheim, University of ´ ¨ Heidelberg, Heidelberg, Germany, 3 Julius Wolff Institut, Berlin-Brandenburg Center for Regenerative Therapies, Charite-Universitatsmedizin Berlin, Berlin, Germany Abstract Background: The TGF family plays a key role in bone homeostasis. Systemic or topic application of proteins of this family apparently positively affects bone healing in vivo. However, patients with chronic inflammation, having increased TGF-b1 serum-levels, often show reduced bone mineral content and disturbed bone healing. Therefore, we wanted to identify intracellular mechanisms induced by chronic presence of TGF-b1 and their possible role in bone homeostasis in primary human osteoblasts. Methodology/Principal Findings: Osteoblasts were isolated from femur heads of patients undergoing total hip replacement. Adenoviral reporter assays showed that in primary human osteoblasts TGF-b1 mediates its signal via Smad2/3 an