Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

[1]  I. Stockley,et al.  The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium , 2021, The bone & joint journal.

[2]  Hyeonjong Lee,et al.  Biomechanical effects of dental implant diameter, connection type, and bone density on microgap formation and fatigue failure: A finite element analysis , 2020, Comput. Methods Programs Biomed..

[3]  M. Odenthal,et al.  Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon , 2020, Scientific Reports.

[4]  M. Nicolov,et al.  Comparative Toxicological In Vitro and In Ovo Screening of Different Orthodontic Implants Currently Used in Dentistry , 2020, Materials.

[5]  Vikki M. Weake,et al.  Gcn5: The quintessential histone acetyltransferase. , 2020, Biochimica et biophysica acta. Gene regulatory mechanisms.

[6]  C. Pina,et al.  Buffering noise: KAT2A modular contributions to stabilization of transcription and cell identity in cancer and development. , 2020, Experimental hematology.

[7]  I. Papatheodorou,et al.  Comparative Transcriptome Analysis of the Regenerating Zebrafish Telencephalon Unravels a Resource With Key Pathways During Two Early Stages and Activation of Wnt/β-Catenin Signaling at the Early Wound Healing Stage , 2020, Frontiers in Cell and Developmental Biology.

[8]  Y. Hu,et al.  F-actin Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through MKL1 and YAP/TAZ , 2020, Nanoscale Research Letters.

[9]  K. Moriyama,et al.  Aberrantly activated Wnt/β‐catenin pathway co‐receptors LRP5 and LRP6 regulate osteoblast differentiation in the developing coronal sutures of an Apert syndrome (Fgfr2S252W/+) mouse model , 2020, Developmental dynamics : an official publication of the American Association of Anatomists.

[10]  Xinchang Zhang,et al.  Schwann Cell-derived exosomes promote bone regeneration and repair by enhancing the biological activity of porous Ti6Al4V scaffolds. , 2020, Biochemical and biophysical research communications.

[11]  Brandon J. Ausk,et al.  A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction , 2020, Nature Communications.

[12]  F. Karadeniz,et al.  3,5-dicaffeoyl‑epi-quinic acid from Atriplex gmelinii enhances the osteoblast differentiation of bone marrow-derived human mesenchymal stromal cells via WnT/BMP signaling and suppresses adipocyte differentiation via AMPK activation. , 2020, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[13]  Yongrong Ji,et al.  Targeting Local Osteogenic and Ancillary Cells by Mechanobiologically Optimized Mg Scaffolds for Orbital Bone Reconstruction in Canines. , 2020, ACS applied materials & interfaces.

[14]  N. Kops,et al.  Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation. , 2019, Acta biomaterialia.

[15]  P. Schmuki,et al.  Lateral Spacing of TiO2 Nanotubes Modulates Osteoblast Behavior , 2019, Materials.

[16]  Huiwu Li,et al.  Mechanical strain promotes osteogenic differentiation of mesenchymal stem cells on TiO2 nanotubes substrate. , 2019, Biochemical and biophysical research communications.

[17]  Zhihui Feng,et al.  Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells , 2019, International journal of molecular sciences.

[18]  Yu Zhu,et al.  Catalpol promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the Wnt/β-catenin pathway , 2019, Stem Cell Research & Therapy.

[19]  Yunchun Li,et al.  Function of GCN5 in the TGF-β1-induced epithelial-to-mesenchymal transition in breast cancer. , 2018, Oncology letters.

[20]  Yubao Li,et al.  Promoting Osseointegration of Ti Implants through Micro/Nanoscaled Hierarchical Ti Phosphate/Ti Oxide Hybrid Coating. , 2018, ACS nano.

[21]  R. McCarthy,et al.  GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation , 2017, Stem cell reports.

[22]  J. K. Leach,et al.  Materials-Directed Differentiation of Mesenchymal Stem Cells for Tissue Engineering and Regeneration. , 2017, ACS biomaterials science & engineering.

[23]  T. Ishimoto,et al.  Effects of mechanical repetitive load on bone quality around implants in rat maxillae , 2017, PloS one.

[24]  Jian-xi Wang,et al.  Tantalum-coated pedicle screws enhance implant integration. , 2017, Colloids and surfaces. B, Biointerfaces.

[25]  Xin Zhao,et al.  Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment. , 2017, Chemical reviews.

[26]  Hua Zhu,et al.  Histone deacetylase-2 is involved in stress-induced cognitive impairment via histone deacetylation and PI3K/AKT signaling pathway modification , 2017, Molecular medicine reports.

[27]  E. Luo,et al.  Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway , 2017, Scientific Reports.

[28]  Fanglong Song,et al.  Mechanical Stress Regulates Osteogenesis and Adipogenesis of Rat Mesenchymal Stem Cells through PI3K/Akt/GSK-3β/β-Catenin Signaling Pathway , 2017, BioMed research international.

[29]  Y. Kido,et al.  The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch , 2016, Nature Communications.

[30]  J. Sun,et al.  GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment , 2016, Scientific Reports.

[31]  M. Brandi,et al.  Densitometric evaluation of bone-prosthetic counterface in hip and knee arthroplasty with modern implants. , 2016, Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases.

[32]  W. Tong,et al.  Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1 , 2016, Cell Death and Disease.

[33]  F. Tang,et al.  Histone Acetyltransferase GCN5 Regulates Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting NF‐κB , 2016, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  K. Schwamborn,et al.  Histone acetylation and histone acetyltransferases show significant alterations in human abdominal aortic aneurysm , 2016, Clinical Epigenetics.

[35]  M. Bennett,et al.  HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis , 2015, Proceedings of the National Academy of Sciences.

[36]  G. Papaccio,et al.  Bone defects: molecular and cellular therapeutic targets. , 2014, The international journal of biochemistry & cell biology.

[37]  K. Ekström,et al.  Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro , 2014, International journal of nanomedicine.

[38]  D. Brann,et al.  Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease , 2013, Brain Research.

[39]  K. Okazaki,et al.  Nuclear Smad7 Overexpressed in Mesenchymal Cells Acts as a Transcriptional Corepressor by Interacting with HDAC-1 and E2F to Regulate Cell Cycle , 2012, Biology Open.

[40]  Suzanne Zeitouni,et al.  Pharmaceutical modulation of canonical Wnt signaling in multipotent stromal cells for improved osteoinductive therapy , 2010, Proceedings of the National Academy of Sciences.

[41]  E. Richards,et al.  Quantitative epigenetics: DNA sequence variation need not apply. , 2009, Genes & development.

[42]  I. Gérin,et al.  Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ* , 2007, Journal of Biological Chemistry.