title: Osteoblast maturation on microtextured titanium involves paracrine regulation of bone morphogenetic protein signaling.
abstract: Osteoblasts are sensitive to surface microtopography and chemistry. Osteoblast differentiation and maturation are higher in vitro and bone formation and osseointegration enhanced in vivo on microstructured titanium (Ti) compared to smooth surfaces. Cells increased BMP2 expression on microtextured Ti alloy, suggesting a paracrine role in regulating osteoblast maturation. However, recent studies show that exogenous BMP2 inhibits osteoblast production of anti-inflammatory cytokines and osteocalcin, indicating that control of BMP-signaling may be involved. This study examined whether cells modulate BMP ligands, receptors, and inhibitors during osteoblast maturation on Ti, specifically focusing on the roles of BMP2 and Noggin (NOG). mRNA and protein for BMP2, BMP4, and BMP7 and receptors BMPR1A, BMPR1B, and BMPR2, and BMP inhibitors were upregulated on microtextured surfaces in comparison to smooth surfaces. Maturation on microstructured Ti was slightly enhanced with exogenous BMP2 while NOG addition inhibited osteoblast maturation. Cells with NOG knocked down significantly increased osteoblast maturation. These results demonstrate that BMP-related molecules are controlled during osteoblast maturation on microstructured Ti surfaces and that endogenous NOG is an important regulator of the process. Modifying paracrine BMP signaling may yield more robust bone formation than application of exogenous BMPs.
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, 23284.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.forename: Qingfen
authors.initials: Q
authors.lastname: Pan
authors.forename: Ginger
authors.initials: G
authors.lastname: Dunn
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Williams
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D000293:Adolescent; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D019899:Paracrine Communication / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology*; D000099176:Noggin Protein
chemical_list: D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D014025:Titanium; D000099176:Noggin Protein
keywords: bone morphogenetic protein; cell signaling; osteoblasts; surface roughness; titanium
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