TY - JOUR
T1 - Bone Morphogenetic Protein 2 Alters Osteogenesis and Anti-Inflammatory Profiles of Mesenchymal Stem Cells Induced by Microtextured Titanium in Vitro
AU - Hyzy, Sharon L.
AU - Olivares-Navarrete, Rene
AU - Ortman, Sarah
AU - Boyan, Barbara D.
AU - Schwartz, Zvi
N1 - Funding Information:
This study was supported by grant 798_2011 from the ITI Foundation for the Promotion of Implantology, Basel, Switzerland. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number AR052102. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding sources played no role in study design; collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. Institut Straumann AG (Basel, Switzerland) provided Ti disks as a gift.
Funding Information:
S.L.H. and S.O. have no competing financial interests to disclose. B.D.B. and Z.S. are unpaid consultants for Institut Straumann AG. R.O.-N., B.D.B., and Z.S. have grant funds from Institut Straumann AG. Z.S. is a paid consultant for AB Dental (Ashdod, Israel). B.D.B. is a paid consultant for Titan Spine LLC (Mequon, WI).
PY - 2017/10
Y1 - 2017/10
N2 - Objectives: Microtextured titanium (Ti) induces osteoblast differentiation of mesenchymal stem cells (MSCs) in the absence of exogenous osteogenic factors; and high-energy surface modifications speed healing of microrough Ti implants. Bone morphogenetic protein 2 (BMP2) is used clinically to improve peri-implant bone formation and osseointegration but can cause inflammation and bone-related complications. In this study, we determined whether BMP2 alters human MSC differentiation, apoptosis, and inflammatory factor production when grown on Ti implants with different surface properties. Materials and Methods: Human MSCs were cultured on Ti substrates (smooth [PT], sandblasted acid-etched [SLA], hydrophilic-SLA [modSLA]), or tissue culture polystyrene (TCPS). After 7 days, inflammatory mRNAs were measured by polymerase chain reaction array. In addition, 7-day cultures were treated with exogenous BMP2 and osteogenic differentiation and production of local factors, proinflammatory interleukins, and anti-inflammatory interleukins assessed. Finally, osteogenic markers and interleukins were measured in MSCs cultured for 48 h on BMP2 dip-coated SLA and modSLA surfaces. Results: Expression of interleukins, chemokines, cytokines, and growth factors was affected by surface properties, particularly on modSLA. MSCs on Ti produced fewer resorptive and more osteogenic/anti-inflammatory factors than cells on TCPS. Addition of 100 ng/mL BMP2 not only increased differentiation but also increased proinflammatory and decreased anti-inflammatory/antiresorptive factors. Two hundred nanograms per milliliter BMP2 abolished osteogenesis and dramatically increased pro-osteoclastogenic factors. MSCs cultured on BMP2-dip-coated disks produced similar proinflammatory profiles with inhibited osteogenic differentiation and had increased apoptotic markers at the highest doses. Conclusions: MSCs underwent osteogenesis and regulated inflammatory cytokines on microtextured Ti. Exogenous BMP2 inhibited MSC differentiation and stimulated a dose-dependent proinflammatory and apoptotic response. Use of BMP2 with microtextured metal implants may increase inflammation and possibly delay bone formation dependent on dose, suggesting that application of BMP2 clinically during implant insertion may need to be reevaluated.
AB - Objectives: Microtextured titanium (Ti) induces osteoblast differentiation of mesenchymal stem cells (MSCs) in the absence of exogenous osteogenic factors; and high-energy surface modifications speed healing of microrough Ti implants. Bone morphogenetic protein 2 (BMP2) is used clinically to improve peri-implant bone formation and osseointegration but can cause inflammation and bone-related complications. In this study, we determined whether BMP2 alters human MSC differentiation, apoptosis, and inflammatory factor production when grown on Ti implants with different surface properties. Materials and Methods: Human MSCs were cultured on Ti substrates (smooth [PT], sandblasted acid-etched [SLA], hydrophilic-SLA [modSLA]), or tissue culture polystyrene (TCPS). After 7 days, inflammatory mRNAs were measured by polymerase chain reaction array. In addition, 7-day cultures were treated with exogenous BMP2 and osteogenic differentiation and production of local factors, proinflammatory interleukins, and anti-inflammatory interleukins assessed. Finally, osteogenic markers and interleukins were measured in MSCs cultured for 48 h on BMP2 dip-coated SLA and modSLA surfaces. Results: Expression of interleukins, chemokines, cytokines, and growth factors was affected by surface properties, particularly on modSLA. MSCs on Ti produced fewer resorptive and more osteogenic/anti-inflammatory factors than cells on TCPS. Addition of 100 ng/mL BMP2 not only increased differentiation but also increased proinflammatory and decreased anti-inflammatory/antiresorptive factors. Two hundred nanograms per milliliter BMP2 abolished osteogenesis and dramatically increased pro-osteoclastogenic factors. MSCs cultured on BMP2-dip-coated disks produced similar proinflammatory profiles with inhibited osteogenic differentiation and had increased apoptotic markers at the highest doses. Conclusions: MSCs underwent osteogenesis and regulated inflammatory cytokines on microtextured Ti. Exogenous BMP2 inhibited MSC differentiation and stimulated a dose-dependent proinflammatory and apoptotic response. Use of BMP2 with microtextured metal implants may increase inflammation and possibly delay bone formation dependent on dose, suggesting that application of BMP2 clinically during implant insertion may need to be reevaluated.
KW - bone morphogenetic protein 2
KW - interleukins
KW - microtexture
KW - stem cells
KW - titanium
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U2 - 10.1089/ten.tea.2017.0003
DO - 10.1089/ten.tea.2017.0003
M3 - Article
C2 - 28351289
AN - SCOPUS:85031996741
VL - 23
SP - 1132
EP - 1141
JO - Tissue Engineering - Part A.
JF - Tissue Engineering - Part A.
SN - 1937-3341
IS - 19-20
ER -