Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis

Autor: Jingwei Zhang, Huipin Yuan, E.J. Vrij, Lorenzo Moroni, Xiaoman Luo, J. Paul Chapple, Davide Barbieri, Martin M. Knight, Melis T. Dalbay, Clemens van Blitterswijk, Joost D. de Bruijn
Přispěvatelé: Biomaterials Science and Technology, CTR, RS: MERLN - Complex Tissue Regeneration (CTR), Division Instructive Biomaterials Eng, RS: MERLN - Instructive Biomaterials Engineering (IBE)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Axoneme
Calcium Phosphates
Pathology
Ceramics
Topography
BONE-GRAFT SUBSTITUTES
02 engineering and technology
Calcium phosphate ceramic
Biochemistry
Primary cilia
Osteogenesis
Mesenchymal stromal cell
Cilium
General Medicine
021001 nanoscience & nanotechnology
DEXAMETHASONE
Cell biology
DIFFERENTIATION
SHAPE
Stem cell
0210 nano-technology
Biotechnology
EXPRESSION
medicine.medical_specialty
Stromal cell
Materials science
FIBRONECTIN
Biomedical Engineering
chemistry.chemical_element
Bone Marrow Cells
Calcium
MESENCHYMAL STEM-CELLS
Biomaterials
03 medical and health sciences
TGFβ
Dogs
TGF beta
Full Length Article
medicine
Animals
Humans
Cilia
Bone
Molecular Biology
Actin
ComputingMethodologies_COMPUTERGRAPHICS
LINEAGE COMMITMENT
Mesenchymal stem cell
IN-VITRO
030104 developmental biology
chemistry
Stromal Cells
Receptors
Transforming Growth Factor beta
Transforming growth factor
Zdroj: Acta biomaterialia, 57, 487-497. Elsevier
Acta Biomaterialia
Acta Biomaterialia, 57, 487-497. Elsevier / Bunge
ISSN: 1742-7061
Popis: Graphical abstract
The surface topography of synthetic biomaterials is known to play a role in material-driven osteogenesis. Recent studies show that TGFβ signalling also initiates osteogenic differentiation. TGFβ signalling requires the recruitment of TGFβ receptors (TGFβR) to the primary cilia. In this study, we hypothesize that the surface topography of calcium phosphate ceramics regulates stem cell morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation. We developed a 2D system using two types of tricalcium phosphate (TCP) ceramic discs with identical chemistry. One sample had a surface topography at micron-scale (TCP-B, with a bigger surface structure dimension) whilst the other had a surface topography at submicron scale (TCP-S, with a smaller surface structure dimension). In the absence of osteogenic differentiation factors, human bone marrow stromal cells (hBMSCs) were more spread on TCP-S than on TCP-B with alterations in actin organization and increased primary cilia prevalence and length. The cilia elongation on TCP-S was similar to that observed on glass in the presence of osteogenic media and was followed by recruitment of transforming growth factor-β RII (p-TGFβ RII) to the cilia axoneme. This was associated with enhanced osteogenic differentiation of hBMSCs on TCP-S, as shown by alkaline phosphatase activity and gene expression for key osteogenic markers in the absence of additional osteogenic growth factors. Similarly, in vivo after a 12-week intramuscular implantation in dogs, TCP-S induced bone formation while TCP-B did not. It is most likely that the surface topography of calcium phosphate ceramics regulates primary cilia length and ciliary recruitment of p-TGFβ RII associated with osteogenesis and bone formation. This bioengineering control of osteogenesis via primary cilia modulation may represent a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery applications. Statement of Significance The surface topography of synthetic biomaterials plays important roles in material-driven osteogenesis. The data presented herein have shown that the surface topography of calcium phosphate ceramics regulates mesenchymal stromal cells (e.g., human bone marrow mesenchymal stromal cells, hBMSCs) with respect to morphology, primary cilia structure and TGFβR recruitment to the cilium associated with osteogenic differentiation in vitro. Together with bone formation in vivo, our results suggested a new type of biomaterial-based ciliotherapy for orthopedic, dental and maxillofacial surgery by the bioengineering control of osteogenesis via primary cilia modulation.
Databáze: OpenAIRE
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