Dataset Information

Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces.

ABSTRACT: Successful osseointegration of an endosseous implant involves migration and differentiation of mesenchymal stem cells (MSCs) on the implant surface. Micro-structured, hydrophilic titanium surfaces direct MSCs to undergo osteoblastic differentiation in vitro, in the absence of media additives commonly used in cultures grown on tissue culture polystyrene (TCPS). This process involves non-canonical Wnt5a, in contrast to canonical Wnt3a typically credited with osteoblastic differentiation on TCPS. Wnt proteins have been implicated in morphological development and tissue patterning, suggesting that additional Wnts may participate. Here, we demonstrate that Wnt11 is a mediator of osteoblast commitment of MSCs, and increases in a surface-roughness dependent manner. Experiments using cells silenced for Wnt11 indicate that cross-talk between Wnt5a and Wnt11 occurs. Wnt11 potentially acts upstream to Wnt5a, increasing Wnt5a expression and factors associated with osteogenesis. Thus, Wnt11 contributes to peri-implant bone formation distal to the implant surface through a heavily regulated signaling cascade of autocrine/paracrine proteins.

SUBMITTER: Boyan BD

PROVIDER: S-EPMC5988747 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces.

Boyan Barbara D BD Olivares-Navarrete Rene R Berger Michael B MB Hyzy Sharon L SL Schwartz Zvi Z

Scientific reports 20180605 1

Successful osseointegration of an endosseous implant involves migration and differentiation of mesenchymal stem cells (MSCs) on the implant surface. Micro-structured, hydrophilic titanium surfaces direct MSCs to undergo osteoblastic differentiation in vitro, in the absence of media additives commonly used in cultures grown on tissue culture polystyrene (TCPS). This process involves non-canonical Wnt5a, in contrast to canonical Wnt3a typically credited with osteoblastic differentiation on TCPS. W ...[more]

PMID: 29872092

Similar Datasets

Project description:Peri-implant bone formation depends on the ability of mesenchymal stem cells (MSCs) to colonize implant surfaces and differentiate into osteoblasts, but the precise mechanisms controlling this process remain unclear. In vitro, MSCs undergo osteoblastic differentiation on microstructured titanium (Ti) surfaces in the absence of exogenous media supplements and produce factors that promote osteogenesis while regulating osteoclast activity, including semaphorins. The goal of this study was to evaluate the role of semaphorin 3A (Sema3A) on surface-mediated osteoblastic differentiation and determine the hierarchy of this signaling cascade. Human MSCs were cultured on 15 mm grade 2 smooth (pretreatment, PT), hydrophobic-microrough (sand blasted/acid etched, SLA), hydrophilic-microrough Ti (mSLA) (Institut Straumann AG, Basel, Switzerland), or tissue culture polystyrene (TCPS). Expression of SEMA3A family proteins increased after 7 days of culture, and the increased expression in response to microstructured Ti was dependent on recognition of the surface by integrin α2β1. Exogenous Sema3A increased differentiation whereas differentiation was decreased in cells treated with a Sema3A antibody. Furthermore, Sema3A influenced the production of osteoprotegerin and osteopontin suggesting it as an important local regulator of bone remodeling. Inhibition of Wnt3A and Wnt5A revealed that activation of Sema3A occurs downstream of Wnt5A and may facilitate the translocation of β-catenin bypassing the canonical Wnt3A initiating signal associated with osteoblastic differentiation. Furthermore, chemical inhibition of calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase (CaMKII), phospholipase A2 (PLA2), protein kinase C (PKC), and BMP receptors suggest that Sema3A could serve as a feedback mechanism for both Wnt5A and BMP2. Here, we show novel roles for Sema3A family proteins in the surface-dependent modulation of MSCs as well as important interactions with pathways known to be associated with osteoblastic differentiation. Moreover, their effects on bone remodeling markers have significant implications for peri-implant bone remodeling and downstream modulation of osteoclastic activity. These results suggest that Sema3A aids in peri-implant bone formation through regulation on multiple stages of osseointegration, making it a potential target to promote osseointegration in patients with compromised bone remodeling.

Project description:Hydroxyapatite (HA), the principal component of bone mineral, shows osteoconductive properties when employed for coating metal implants as well as scaffold materials in synthetic bone grafts. With the goal of providing this material with osteoinductive capabilities to promote faster bone regeneration, we show an easy approach to functionalize HA implant surfaces and enrich them with osteoinductive properties by the use of HA-binding modular peptides. The modular peptides are designed as a combination of two domains, an HA-binding peptide motif and an osteogenic peptide motif derived from the osteogenic growth peptide (OGP) or bone morphometric protein 7 (BMP-7). To identify the best HA-binding peptide, several nature-inspired peptides derived from natural bone extracellular matrix proteins (bone sialoprotein, osteonectin, osteocalcin, and salivarin statherin) were compared for HA-binding activity, revealing concentration-dependent and incubation-time-dependent behaviours. We discovered that a Poly-E heptamer (E7) is the best HA-binding peptide, and thus combined it with a second osteogenic peptidic domain to create an osteoinductive modular peptide. After binding/release characterization, we found that the addition of the second osteogenic peptide domain did not change the binding profile of the modular peptides and caused only a slight change in their release kinetics. Mesenchymal stem cells (MSCs) were cultured on the HA substrates functionalized with modular peptides, and cell adhesion, proliferation, and differentiation in a basal medium (i.e., without any osteogenic supplements) were investigated. Gene expression data clearly showed that MSCs were committed to differentiate into osteoblasts in the presence of the modular peptides. HA discs functionalized with the E7 BMP-7 modular peptide showed the best capability in inducing the osteogenic differentiation of MSCs among all modular peptides studied. The modular peptides can easily be used to functionalize the HA implants through its constituent HA-binding motif, leaving the osteogenic peptide motif protruding from the surface for inducing osteogenesis. Our work opens up a new approach to the formulation of new bioactive HA coatings and implants for bone and dental repair.

Project description:The repair and replacement of damaged or diseased human bone tissue requires a stable interface between the orthopedic implant and living tissue. The ideal material should be both osteoconductive (promote bonding to bone) and osteoinductive (induce osteogenic differentiation of cells and generate new bone). Partially resorbable bioceramic materials with both properties are developed by expensive trial-and-error methods. Structure-reactivity relationships for predicting the osteoinductive properties of ceramics would significantly increase the efficiency of developing materials for bone tissue engineering. Here we propose the novel hypothesis that the crystal structure of a bioceramic controls the release rates, subsequent surface modifications due to precipitation of new phases, and thus, the concentrations of soluble factors, and ultimately, the attachment, viability and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). To illustrate our hypothesis, we used two CaSiO3 polymorphs, pseudo-wollastonite (psw, ?-CaSiO3) and wollastonite (wol, ?-CaSiO3) as scaffolds for hMSC culture. Polymorphs are materials which have identical chemical composition and stoichiometry, but different crystal structures. We combined the results of detailed surface characterizations, including environmental Scanning Electron Microscopy (SEM) back-scattered imaging, and spot-analysis and 2D elemental mapping by SEM-Energy Dispersive X-ray (SEM-EDX), High Resolution Transmission Electron Microscopy (HRTEM) and surface roughness analysis; culture medium solution analyses; and molecular/genetic assays from cell culture. Our results confirmed the hypothesis that the psw polymorph, which has a strained silicate ring structure, is more osteoinductive than the wol polymorph, which has a more stable, open silicate chain structure. The observations could be attributed to easier dissolution (resorption) of psw compared to wol, which resulted in concentration profiles that were more osteoinductive for the former. Thus, we showed that crystal structure is a fundamental parameter to be considered in the intelligent design of pro-osteogenic, partially resorbable bioceramics.

Dataset Information

Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces.

Publications

Role of Wnt11 during Osteogenic Differentiation of Human Mesenchymal Stem Cells on Microstructured Titanium Surfaces.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets