Mediation of osteogenic differentiation of human mesenchymal stem cells on titanium surfaces by a Wnt-integrin feedback loop

Olivares-Navarrete, René; Hyzy, Sharon L.; Park, Jung Hwa; Dunn, Ginger R.; Haithcock, David A.; Wasilewski, Christine E.; Boyan, Barbara D.; Schwartz, Zvi

doi:10.1016/j.biomaterials.2011.05.036

Cited by 131 publications

(131 citation statements)

References 47 publications

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“…In the present study, Wnt5a levels increased in response to TNF-a in human differentiating osteoblasts. We also report that Wnt5a stimulated TNAP activity in hu- man osteoblasts [28,40,41]. We hypothesize that Wnt5a stimulates TNAP and mineralization through inhibition of PPAR activity in osteoblasts [25,30].…”

Section: Discussionsupporting

confidence: 54%

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Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Briolay

Lencel²,

Bessueille

et al. 2013

Biochemical and Biophysical Research Communications

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a b s t r a c tAlthough anti-tumor necrosis factor (TNF)-a treatments efficiently block inflammation in ankylosing spondylitis (AS), they are inefficient to prevent excessive bone formation. In AS, ossification seems more prone to develop in sites where inflammation has resolved following anti-TNF therapy, suggesting that TNF-a indirectly stimulates ossification. In this context, our objectives were to determine and compare the involvement of Wnt proteins, which are potent growth factors of bone formation, in the effects of TNF-a on osteoblast function. In human mesenchymal stem cells (MSCs), TNF-a significantly increased the levels of Wnt10b and Wnt5a. Associated with this effect, TNF-a stimulated tissue-non specific alkaline phosphatase (TNAP) and mineralization. This effect was mimicked by activation of the canonical bcatenin pathway with either anti-Dkk1 antibodies, lithium chloride (LiCl) or SB216763. TNF-a reduced, and activation of b-catenin had little effect on expression of osteocalcin, a late marker of osteoblast differentiation. Surprisingly, TNF-a failed to stabilize b-catenin and Dkk1 did not inhibit TNF-a effects. In fact, Dkk1 expression was also enhanced in response to TNF-a, perhaps explaining why canonical signaling by Wnt10b was not activated by TNF-a. However, we found that Wnt5a also stimulated TNAP in MSCs cultured in osteogenic conditions, and increased the levels of inflammatory markers such as COX-2. Interestingly, treatment with anti-Wnt5a antibodies reduced endogenous TNAP expression and activity. Collectively, these data suggest that increased levels of Dkk1 may blunt the autocrine effects of Wnt10b, but not that of Wnt5a, acting through non-canonical signaling. Thus, Wnt5a may be potentially involved in the effects of inflammation on bone formation.

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Section: Discussionsupporting

confidence: 54%

“…Wnt5a, Dkk1 and anti-Dkk1 antibodies were purchased from R&D Systems (Lille, France). We used mouse Wnt5a, which shares 97% homology with human Wnt5a and is biologically active in human cells [28]. Anti-Wnt5a antibodies were from Santa-Cruz (Heidelberg, Germany).…”

Section: Chemicalsmentioning

confidence: 99%

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Briolay

Lencel²,

Bessueille

et al. 2013

Biochemical and Biophysical Research Communications

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“…Similar observations have been reported in several different TiO 2 dental implant surfaces in in vitro and in vivo rat tibia studies. 11,[35][36][37][38] The proposed mechanism of titanium-associated osteoinduction is thought to be related to hydroxyl groups and calcium ions present in TiO 2 surfaces. These hydroxyl groups may well promote adsorption of calcium-binding extracellular matrix proteins (e.g., alkaline phosphatase) and RGD-specific peptide sequences (e.g., fibronectin, bone sialoprotein).…”

Section: Discussionmentioning

confidence: 99%

“…10 Titania additives may constitute an advantage by increasing surface hydrophobicity and protein adsorption to further enhance cell adhesion, osteogenic induction, and formability in bone biomaterials, including in HAP-GEL. 7,11,12 Consequently, bone regeneration of formable titanium dioxide (TiO 2 )-enriched HAP-GEL scaffolds was compared in this study to HAP-GEL alone.…”

Section: Introductionmentioning

confidence: 99%

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

Ferreira

Padilla

Urkasemsin

et al. 2013

Tissue Engineering Part A

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Adequate bony support is the key to re-establish both function and esthetics in the craniofacial region. Autologous bone grafting has been the gold standard for regeneration of problematic large bone defects. However, poor graft availability and donor-site complications have led to alternative bone tissue-engineering approaches combining osteoinductive biomaterials and three-dimensional cell aggregates in scaffolds or constructs. The goal of the present study was to generate novel cell aggregate-loaded macroporous scaffolds combining the osteoinductive properties of titanium dioxide (TiO 2 ) with hydroxyapatite-gelatin nanocomposites (HAP-GEL) for regeneration of craniofacial defects. Here we investigated the in vivo applicability of macroporous (TiO 2 )-enriched HAP-GEL scaffolds with undifferentiated and osteogenically differentiated multipotent adult progenitor cell (MAPC and OD-MAPC, respectively) aggregates for calvaria bone regeneration. The silane-coated HAP-GEL with and without TiO 2 additives were polymerized and molded to produce macroporous scaffolds. Aggregates of the rat MAPC were precultured, loaded into each scaffold, and implanted to rat calvaria criticalsize defects to study bone regeneration. Bone autografts were used as positive controls and a poly(lacticco-glycolic acid) (PLGA) scaffold for comparison purposes. Preimplanted scaffolds and calvaria bone from pig were tested for ultimate compressive strength with an Instron 4411 Ò and for porosity with microcomputerized tomography (mCT). Osteointegration and newly formed bone (NFB) were assessed by mCT and nondecalcified histology, and quantified by calcium fluorescence labeling. Results showed that the macroporous TiO 2 -HAP-GEL scaffold had a comparable strength relative to the natural calvaria bone (13.8 -4.5 MPa and 24.5 -8.3 MPa, respectively). Porosity was 1.52 -0.8 mm and 0.64 -0.4 mm for TiO 2 -HAP-GEL and calvaria bone, respectively. At 8 and 12 weeks postimplantation into rat calvaria defects, greater osteointegration and NFB were significantly present in the TiO 2 -enriched HAP-GEL constructs with OD-MAPCs, compared to the undifferentiated MAPCloaded constructs, cell-free HAP-GEL with and without titanium, and PLGA scaffolds. The tissue-engineered TiO 2 -enriched HAP-GEL constructs with OD-MAPC aggregates present a potential useful therapeutic approach for calvaria bone regeneration.

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“…As a consequence, nonphosphorylated β-catenin from the destruction complex and FRAT1 translocate into the nucleus to react with TCF/LEF transcription factors and regulate downstream genes, including those involved in bone formation, such as Runx2, Col-1, and OPN is induced. 49 It has been reported that Wnt/β-catenin signaling pathway mediates the biological effects of the microstructured titanium surface, 50,51 while the accumulated data suggests that activation of Wnt signaling is required for regeneration of periodontal tissues such as cementum, periodontal ligament, and alveolar bone. 25,52 Also, it has been reported that temporospatial regulation of Wnt/β-catenin signaling plays an important role in cell differentiation and matrix formation during root and cementum formation.…”

mentioning

confidence: 99%

Effect of micro-nano-hybrid structured hydroxyapatite bioceramics on osteogenic and cementogenic differentiation of human periodontal ligament stem cell via Wnt signaling pathway

Mao¹,

Liu²,

Zhao³

et al. 2015

IJN

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The surface structure of bioceramic scaffolds is crucial for its bioactivity and osteoinductive ability, and in recent years, human periodontal ligament stem cells have been certified to possess high osteogenic and cementogenic differential ability. In the present study, hydroxyapatite (HA) bioceramics with micro-nano-hybrid surface (mnHA [the hybrid of nanorods and microrods]) were fabricated via hydrothermal reaction of the α-tricalcium phosphate granules as precursors in aqueous solution, and the effects of mnHA on the attachment, proliferation, osteogenic and cementogenic differentiations of human periodontal ligament stem cells as well as the related mechanisms were systematically investigated. The results showed that mnHA bioceramics could promote cell adhesion, proliferation, alkaline phosphatase (ALP) activity, and expression of osteogenic/cementogenic-related markers including runt-related transcription factor 2 (Runx2), ALP, osteocalcin (OCN), cementum attachment protein (CAP), and cementum protein (CEMP) as compared to the HA bioceramics with flat and dense surface. Moreover, mnHA bioceramics stimulated gene expression of low-density lipoprotein receptor-related protein 5 ( LRP5 ) and β-catenin , which are the key genes of canonical Wnt signaling. Moreover, the stimulatory effect on ALP activity and osteogenic and cementogenic gene expression, including that of ALP, OCN, CAP, CEMP, and Runx2 of mnHA bioceramics could be repressed by canonical Wnt signaling inhibitor dickkopf1 (Dkk1). The results suggested that the HA bioceramics with mnHA could act as promising grafts for periodontal tissue regeneration.

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Mediation of osteogenic differentiation of human mesenchymal stem cells on titanium surfaces by a Wnt-integrin feedback loop

Cited by 131 publications

References 47 publications

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

Effect of micro-nano-hybrid structured hydroxyapatite bioceramics on osteogenic and cementogenic differentiation of human periodontal ligament stem cell via Wnt signaling pathway

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