title: Response of a preosteoblastic cell line to cyclic tensile stress conditioning and growth factors for bone tissue engineering.
abstract: Bone regeneration can be accelerated by utilizing mechanical stress and growth factors (GFs). However, a limited understanding exists regarding the response of preosteoblasts to tensile stress alone or with GFs. We measured cell proliferation and expression of heat-shock proteins (HSPs) and other bone-related proteins by preosteoblasts following cyclic tensile stress (1%-10% magnitude) alone or in combination with bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1). Tensile stress (3%) with GFs induced greater gene upregulation of osteoprotegerin (3.3 relative fold induction [RFI] compared to sham-treated samples), prostaglandin E synthase 2 (2.1 RFI), and vascular endothelial growth factor (VEGF) (11.5 RFI), compared with samples treated with stimuli alone or sham-treated samples. The most significant increases in messenger RNA expression occurred with GF addition to either static-cultured or tensile-loaded (1% elongation) cells for the following genes: HSP47 (RFI=2.53), cyclooxygenase-2 (RFI=72.52), bone sialoprotein (RFI=11.56), and TGF-β1 (RFI=8.05). Following 5% strain with GFs, VEGF secretion increased 64% (days 3-6) compared with GF alone and cell proliferation increased 23% compared with the sham-treated group. GF addition increased osteocalcin secretion but decreased matrix metalloproteinase-9 significantly (days 3-6). Tensile stress and GFs in combination may enhance bone regeneration by initiating angiogenic and anti-osteoclastic effects and promote cell growth.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Eunna
authors.initials: E
authors.lastname: Chung
authors.forename: Marissa Nichole
authors.initials: MN
authors.lastname: Rylander
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A