Substrate modulus regulates osteogenic differentiation of rat mesenchymal stem cells through integrin β1 and BMP receptor type IA

Ru, Guo; Lu, Sichang; Merkel, Alyssa R.; Sterling, Julie A.; Guelcher, Scott A.

doi:10.1039/c5tb02747k

Cited by 14 publications

(13 citation statements)

References 48 publications

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“…Neural differentiation is favored in soft substrate, whereas moderate substrate stiffness appreciates chondrogenic differentiation. Similarly, the stiffer substrate encourages osteogenic differentiation in stem cells [111][112][113]. These results suggested that the elastic modulus of native tissue is similar to the elastic modulus of stem cell differentiation; thereby, osteogenic differentiation is favored when a stiff scaffold is used [114].…”

Section: Interventions In Actin Remodeling and Their Effect On Msc DImentioning

confidence: 86%

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

Khan

Fan

et al. 2020

Stem Cell Res Ther

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Mesenchymal stem cells (MSCs) have the capacity to differentiate into multiple lineages including osteogenic and adipogenic lineages. An increasing number of studies have indicated that lineage commitment by MSCs is influenced by actin remodeling. Moreover, actin has roles in determining cell shape, nuclear shape, cell spreading, and cell stiffness, which eventually affect cell differentiation. Osteogenic differentiation is promoted in MSCs that exhibit a large spreading area, increased matrix stiffness, higher levels of actin polymerization, and higher density of stress fibers, whereas adipogenic differentiation is prevalent in MSCs with disrupted actin networks. In addition, the mechanical properties of F-actin empower cells to sense and transduce mechanical stimuli, which are also reported to influence differentiation. Various biomaterials, mechanical, and chemical interventions along with pathogeninduced actin alteration in the form of polymerization and depolymerization in MSC differentiation were studied recently. This review will cover the role of actin and its modifications through the use of different methods in inducing osteogenic and adipogenic differentiation.

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Section: Interventions In Actin Remodeling and Their Effect On Msc DImentioning

confidence: 86%

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

Khan

Fan

et al. 2020

Stem Cell Res Ther

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“…MSCs with a small surface area (Frith, Mills, & Cooper-White, 2012;Guo, Lu, Merkel, Sterling, & Guelcher, 2016;Koçer & Jonkheijm, 2017;Wang et al, 2013). Therefore, for studies investigating the Cells on SLBs with 0.5 μM RGD showed more phospho-paxillin clusters than on SLBs with 0.2 or 1.0 μM RGD.…”

Section: Ligand Mobility and Density On Rgdfunctionalized Slbs Affementioning

confidence: 99%

“…MSCs with a small surface area (Frith, Mills, & Cooper-White, 2012;Guo, Lu, Merkel, Sterling, & Guelcher, 2016;Koçer & Jonkheijm, 2017;Wang et al, 2013). Therefore, for studies investigating the effect of substrate stiffness and ligand presentation on preosteoblast morphology, it should be established whether there is a relation between pre-osteoblast morphology and the osteogenic state.…”

Section: Ligand Mobility and Density On Rgdfunctionalized Slbs Affementioning

confidence: 99%

“…These signaling molecules activate signaling pathways such as mitogen-activated protein kinase, which play a critical role in osteogenic differentiation of MSCs by stimulating RUNX2 gene expression (Khatiwala et al, 2009;Marie et al, 2014). MSCs with large focal adhesions are more osteogenic than cells with small focal adhesions (Frith et al, 2012;Guo et al, 2016;Koçer & Jonkheijm, 2017;Wang et al, 2013). MC3T3-E1 pre-osteoblasts show increased focal adhesion formation accompanied by decreased osteocalcin expression and matrix mineralization (Kong, Polte, Alsberg, & Mooney, 2005).…”

Section: Ligand Mobility and Density On Rgdfunctionalized Slbs Affementioning

confidence: 99%

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RGD‐functionalized supported lipid bilayers modulate pre‐osteoblast adherence and promote osteogenic differentiation

Verstappen

Jin

Koçer

et al. 2020

J Biomedical Materials Res

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Biomaterial integration into bone requires optimal surface conditions to promote osteoprogenitor behavior, which is affected by integrin-binding via arginine-glycine-aspartate (RGD). RGD-functionalized supported lipid bilayers (SLBs) might be interesting as biomaterial coating in bone regeneration, because they allow integration of proteins, for example, growth factors, cytokines, and/or antibacterial agents. Since it is unknown whether and how they affect osteoprogenitor adhesion and differentiation, the aim was to investigate adhesion, focal adhesion formation, morphology, proliferation, and osteogenic potential of pre-osteoblasts cultured on RGD-functionalized SLBs compared to unfunctionalized SLBs and poly-L-lysine (PLL). After 17 hr, pre-osteoblast density on SLBs without or with RGD was similar, but lower than on PLL. Cell surface area, elongation, and number and size of phospho-paxillin clusters were also similar. Cells on SLBs without or with RGD were smaller, more elongated, and had less and smaller phospho-paxillin clusters than on PLL. OPN expression was increased on SLBs with RGD compared to PLL. Moreover, after 1 week, COL1a1 expression was increased on SLBs without or with RGD. In conclusion, pre-osteoblast adhesion and enhanced differentiation were realized for the first time on RGD-functionalized SLBs, pointing to a new horizon in the management of bone regeneration using biomaterials. Together with SLBs nonfouling nature and the possibility of adjusting SLB fluidity and peptide content make SLBs highly promising as substrate to develop innovative biomimetic coatings for biomaterials in bone regeneration.

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“…We previously reported that the substrate modulus of 2D films regulates tumor cell expression of the transcription factor Gli2 and parathyroid hormone-related protein ( PTHrP ), both of which have been associated with bone destruction [ 5 , 6 ]. However, in the 3D bone microenvironment, cells are exposed to mechanical forces resulting from surface curvature [ 26 ] in addition to the substrate modulus, which stimulates mechanically transduced signaling in tumor [ 6 ] and bone [ 27 , 28 ] cells. To more accurately recapitulate the mechanical and morphometric properties of the bone microenvironment, we fabricated 3D scaffolds with tunable substrate moduli and pore size using a templated-Fused Deposition Modeling (3D t-FDM) process [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

3D Bone Morphology Alters Gene Expression, Motility, and Drug Responses in Bone Metastatic Tumor Cells

Dadwal

Merkel

Page

et al. 2020

IJMS

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Patients with advanced skeletal metastases arising from primary cancers including breast, lung, and prostate suffer from extreme pain, bone loss, and frequent fractures. While the importance of interactions between bone and tumors is well-established, our understanding of complex cell–cell and cell–microenvironment interactions remains limited in part due to a lack of appropriate 3D bone models. To improve our understanding of the influence of bone morphometric properties on the regulation of tumor-induced bone disease (TIBD), we utilized bone-like 3D scaffolds in vitro and in vivo. Scaffolds were seeded with tumor cells, and changes in cell motility, proliferation, and gene expression were measured. Genes associated with TIBD significantly increased with increasing scaffold rigidity. Drug response differed when tumors were cultured in 3D compared to 2D. Inhibitors for Integrin β3 and TGF-β Receptor II significantly reduced bone-metastatic gene expression in 2D but not 3D, while treatment with the Gli antagonist GANT58 significantly reduced gene expression in both 2D and 3D. When tumor-seeded 3D scaffolds were implanted into mice, infiltration of myeloid progenitors changed in response to pore size and rigidity. This study demonstrates a versatile 3D model of bone used to study the influence of mechanical and morphometric properties of bone on TIBD.

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Substrate modulus regulates osteogenic differentiation of rat mesenchymal stem cells through integrin β1 and BMP receptor type IA

Cited by 14 publications

References 48 publications

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells

RGD‐functionalized supported lipid bilayers modulate pre‐osteoblast adherence and promote osteogenic differentiation

3D Bone Morphology Alters Gene Expression, Motility, and Drug Responses in Bone Metastatic Tumor Cells

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