title: Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells.
abstract: Long-term stability of arthroplasty prosthesis depends on the integration between osseous tissue and the implant biomaterial. Integrity of the osseous tissue requires the contribution of mesenchymal stem cells and their continuous differentiation into an osteoblastic phenotype. This study aims to investigate the hypothesis that exposure to wear debris particles derived from orthopaedic biomaterials affects the osteoblastic differentiation of human mesenchymal stem cells (hMSC). Upon in vitro culture in the presence of osteogenic supplements (OS), we observe that cultures of hMSCs isolated from femoral head bone marrow are capable of osteogenic differentiation, expressing alkaline phosphatase, osteocalcin, and bone sialoprotein (BSP), in addition to producing collagen type I and BSP accompanied by extracellular matrix mineralization. Exposure of OS-treated hMSCs to submicron commercially pure titanium (cpTi) particles suppresses BSP gene expression, reduces collagen type I and BSP production, decreases cellular proliferation and viability, and inhibits matrix mineralization. In comparison, exposure to zirconium oxide (ZrO2) particles of similar size did not alter osteoblastic gene expression and resulted in only a moderate decrease in cellular proliferation and mineralization. Confocal imaging of cpTi-treated hMSC cultures revealed patchy groups of cells displaying disorganized cytoskeletal architecture and low levels of extracellular BSP. These in vitro findings suggest that chronic exposure of marrow cells to titanium wear debris in vivo may contribute to decreased bone formation at the bone/implant interface by reducing the population of viable hMSCs and compromising their differentiation into functional osteoblasts. Understanding the nature of hMSC bioreactivity to orthopaedic wear debris should provide additional insights into mechanisms underlying aseptic loosening.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Wang
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Nesti
authors.forename: Richard
authors.initials: R
authors.lastname: Tuli
authors.forename: Jovin
authors.initials: J
authors.lastname: Lazatin
authors.forename: Keith G
authors.initials: KG
authors.lastname: Danielson
authors.forename: Peter F
authors.initials: PF
authors.lastname: Sharkey
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000032:analysis / Q000235:genetics; D003599:Cytoskeleton / Q000187:drug effects; D003764:Dental Materials / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects; D005270:Femur Head / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D058574:Integrin-Binding Sialoprotein; D008648:Mesoderm / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000032:analysis / Q000235:genetics; D010641:Phenotype; D011475:Prosthesis Failure; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D014025:Titanium / Q000494:pharmacology*; D015040:Zirconium / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D003764:Dental Materials; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; D015675:Osteocalcin; D015040:Zirconium; D014025:Titanium; D000469:Alkaline Phosphatase; C028541:zirconium oxide