Relationship of matrix stiffness and cell morphology in regulation of osteogenesis and adipogenesis of BMSCs

Abstract

Backgrounds: Both matrix stiffness and cell morphology have been found as important factors directing MSCs (mesenchymal stem cells) differentiation, but cells also spontaneously adapt their morphology under matrix stiffness stimulation. This study aimed to investigate the interplay of cell morphology and matrix stiffness on osteogenesis and adipogenesis of rBMSCs(rat bone BMSCs) on 2D substrates.Methods and Results: First, we modulated MSCs morphology through different bronectin (FN) concentrations on tissue culture plates (TCPs). We found FN promoted and osteogenesis of BMSCs while suppressing adipogenesis, mediated by FN-induced F-actin polymerization and cell spreading. Based on these ndings, we modulated BMSCs morphology on 0.5 kPa and 32 kPa CytoSoft ® plates through FN concentrations. We found BMSCs on 0.5 kPa substrates coated with 300μg/ml of FN manifested similarly spreading morphology with cells on 32 kPa substrates coated with 100 μg/ml of FN, and cells in both groups dominantly commit osteogenesis. On the other hand, BMSCs on 32 kPa substrates coated with 30μg/ml of FN manifested similarly restricted morphology with cells in on 0.5 kPa substrates with 100μg/ml of FN, and in both groups cells mainly commit adipogenesis. Immuno uorescence staining indicated YAP/TAZ mainly located in cytoplasm when cells exhibited restricted morphology on stiff matrices, while exhibiting signi cant nuclear translocation when cells spread on soft matrices.Conclusions: Cell morphology overrode effects of matrix stiffness on BMSCs differentiation through more robust regulation of YAP/TAZ. Matrix stiffness depended on cell morphology to regulate osteogenesis and adipogenesis of BMSCs.

A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

“…[ 34 ] And spindle‐shaped cells have larger spreading areas than round‐shaped cells, while the enlarged spreading area could potentiate the nuclear translocation of YAP/TAZ and regulate the osteogenesis of BMSCs. [ 35 ] Besides, the observed neovascular ingrowth into the osseous region could also account for the endochondral ossification in the lower bone layer of the stratified hydrogel (Figure 4). Vascularization plays an essential role in endochondral ossification that osteoclasts and hematopoietic precursor cells brought during neovascularity infiltration will mediate the absorption of the cartilage anlage, the emergence of the primary ossification center and the final formation of mineralized bone.…”

Pt‐Clusters‐Equipped Antioxidase‐Like Biocatalysts as Efficient ROS Scavengers for Treating Periodontitis

“…After confirming that Pt─CN biocatalyst can protect hMSCs in a high ROS condition, we measure their cell function in terms of stem cell spreading and adhesion. [ 41,42 ] As shown in Figure 3e, stem cells under H 2 O 2 conditions show poor spreading with weak skeleton organization and a round morphology. [ 43,44 ] On the contrary, cells in the Pt H ─CN group show a flattened, normal morphology with a stretched cytoskeleton, while the Pt L ─CN group exhibits weaker cytoskeletal protection than the Pt H ─CN group.…”

Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate In Vitro and Enhances Bone Remodeling In Vivo

“…[ 58 ] However, the 3D static hydrogels with high stiffness restrict the rearrangement of integrins, cell spreading and volume expansion, failing to regulate MSCs differentiation by influencing YAP/TAZ intensity or location. [ 59 ] Therefore, the dynamic stiffening in 3D allows the cell spreading area to increase and cell volume expansion, resulting in the high stiffness after the second crosslinking work.…”