Dopaminergic Enhancement of Cellular Adhesion in Bone Marrow Derived Mesenchymal Stem Cells (MSCs)

Abstract

Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel adhesive protein that has gained increasing attention for its role in cellular growth enhancement in biomaterials, including cellular adhesion improvement. As the mechanism underlying this remains unclear, the objective of this study was to explore the effects of DA on the adhesion properties of bone marrow derived rat mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite biomaterial and to test whether the effects are mediated through various endogenously expressed DA receptors. Primary rMSCs were pretreated with D1-like antagonist, D2-like antagonist, or a combination of these antagonists followed by treatment with 50 μM DA and cellular adhesion quantification at 0.5, 1, 2 and 4 hours post DA addition. DA was found to increase rMSC adhesion and spreading at the 0.5 hour time-point and the dopaminergic effect on cell adhesion was partially blocked by DA antagonists. In addition, the D1-like and D2-like antagonists appeared to have a similar effect on rMSCs. Immunofluorescent staining indicated that the rMSC spreading area was significantly increased in the DA treated group versus the control group. Treatment of the D1-like DA antagonists with DA revealed that the actin filaments of rMSCs could not connect the membrane with the nucleus. In summary, DA was found to enhance early rMSC adhesion partially via DA receptor activation.

<p>Effect of mussel adhesive protein coating on osteogenesis in vitro and osteointegration in vivo to alkali-treated titanium with nanonetwork structures</p>

“…ECM-derived adhesion proteins and growth factors can efficiently attach to surfaces modified with DOPA 44,45. Studies have suggested that rMSC may be induced by nanotopographical signals through FA and actomyosin cytoskeleton contractility 46. The nanostructure and superior hydrophilicity of the surface material also induce cell adhesion 12,13,47–49…”

Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties

“…Thus, the insertion of BNGF seems to exacerbate the effect of osteogenic stimulation. At the same time, the polydopamine coating improves calcium phosphate deposition owing to dopamine’s affinity for chelating calcium ions, thereby enhancing the inherent bioactivity of BGNF. − Thus, the mesoporous and ion-releasing feature of BGNF associated with the osteogenic characteristic of polydopamine coatings inside the SF matrix creates biophysical and biochemical cues capable of promoting significant changes in the organization, morphology, differentiation, and cellular activity of the cytoskeleton.…”

Applications of Polydopamine in Implant Surface Modification

“…[60] Several studies have previously demonstrated that free DA monomers can be detected in the space surrounding PDA. [61] To attain better physical and chemical properties, most researchers have used 150-500 μm DA to form PDA; therefore, a micromolar amount of DA can be expected to be released into the microenvironment around a PDA insertion site. [61][62][63][64][65] Caron et al studied a DA transporter (DAT) knockdown mouse model with which the relationship between DA and bone remodeling was revealed.…”

“…[61] To attain better physical and chemical properties, most researchers have used 150-500 μm DA to form PDA; therefore, a micromolar amount of DA can be expected to be released into the microenvironment around a PDA insertion site. [61][62][63][64][65] Caron et al studied a DA transporter (DAT) knockdown mouse model with which the relationship between DA and bone remodeling was revealed. [66,67] The DAT is an important determinant of DA signaling activity as it is responsible for the rapid uptake of released DA into presynaptic terminals, which effectively removes extracellular DA and terminates its signaling.…”

“…[80,87] In addition, it has been reported that activation of DA receptors by DA could increase the proliferation and adhesion of BMSCs via the integrin-focal adhesion kinase (Itg-FAK) signaling pathway. [61] Wang et al [68] showed that DA enhanced BMSCs via the activation of D1R but not D2R and promoted the phosphorylation of ERK1/2. Zhu et al further confirmed that the activation of D1R reduced dexamethasone (Dex)induced bone loss by activating the ERK1/2 pathway in vivo.…”