Dopamine Suppresses Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells via AKT/GSK-3β/β-Catenin Signaling Pathway

Abstract

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes (Col1a1, Alp, Runx2, Opn, and Ocn). Furthermore, dopamine inactivated AKT/GSK-3β/β-catenin signaling pathway. Treatment of LiCl (GSK-3β inhibitor) rescued the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. LY294002 (AKT inhibitor) administration exacerbated the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. Taken together, these findings indicate that dopamine suppresses osteogenic differentiation of rBMSCs via AKT/GSK-3β/β-catenin signaling pathway. Our study provides new insights into the role of neurotransmitters in bone homeostasis.

lncRNA CYTOR Facilitates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating SOX11 via Sponging miR-6512-3p

“…This is consistent with previous results reported in HeLa cells [10]. ALP activity, expression of RUNX2, Osterix, OCN, and calcified nodules detected by Alizarin red are generally regarded as osteogenic related differentiation markers [18]. They are vastly used to assess osteogenic capability.…”

“…Western Blot Analysis. Western blot was performed as described before [18]. Total proteins were extracted from the cells by RIPA lysis buffer (Beyotime, China) with 1% protease inhibitor (CoWin Biosciences, China).…”

Effects of Dopamine on stem cells and its potential roles in the treatment of inflammatory disorders: a narrative review

“…A recent study by Hong and colleagues supported these findings. They found that dopamine did not interfere with the apoptosis and proliferation of rBMSCs (rat bone marrow mesenchymal stromal cells) at a concentration of 10 μM, but inhibited osteogenic differentiation of rBMSCs through the AKT/GSK-3β/β-Catenin signaling pathway, reduced ALP activity and minimized nodule formation, and decreased expression of osteogenic associated genes ( Col1a1, ALP, Runx2, Opn, and Ocn ) [ 58 ]. These studies indicated that different dopamine concentrations might cause different results in osteogenic differentiation of BMSC.…”

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis

“…Because of the formation of these nerve endings, OA is a chronic pain condition; however, the role of neurotransmitters during OA is just beginning to be understood [ 139 , 140 , 141 , 142 , 143 , 144 ]. Although cartilage lacks nerve endings, chondrocytes have been found to express some catecholamine receptors, and the role of DA during bone formation has been studied in vitro and also in fracture models in adult individuals [ 140 , 145 , 146 ]. Another important aspect in the pathogenesis of OA is inflammation, which is exacerbated in the initial phase of OA, mainly by cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα), which can also contribute to the damage of articular chondrocytes and ultimately to the dedifferentiation of chondrocytes to a fibrocartilaginous phenotype and finally to bone formation [ 144 , 147 , 148 , 149 ].…”