Dopaminergic effects on in vitro osteogenesis
Dong Joon Lee , Henry C Tseng , Sing Wai Wong , Zhengyan Wang , Meng Deng , Ching-Chang Ko
Bone Research ›› 2015, Vol. 3 ›› Issue (1) : 15020
Dopaminergic effects on in vitro osteogenesis
Multiple growth factors (e.g., BMP2, TGF-β1, FGF2) and isolated genes have been shown to improve osteoblastic proliferation and mineralization, advancing bone tissue engineering. Among these factors, both polydopamine (PDA) and dopamine (DA) monomer have recently been reported to increase osteoblast proliferation and mineralization in vitro. Although a well-characterized neurotransmitter, DA’s role in the bone is unknown. We hypothesize that DA can directly act on osteoblasts, and examined whether osteoblasts express DA receptors that respond to exogenous DA. mRNAs and protein cell lysates were obtained from MC3T3-E1 cells during osteogenic differentiation phase. Reverse transcription polymerase chain reaction and western blot analysis were used to examine the expression of DA receptors, D1–D5. Dose-response effect and time course of DA treatment on cell proliferation, mineralization, and osteogenic differentiation were investigated at pre-determined days. Real-time PCR was performed to investigate whether DA affects osteogenic gene expression (ALP, BSP, OC, OSX, RUNX2, and Collagen1a2) with or without receptor antagonists (SCH233390 and GR103691). Two-way ANOVA was used for statistical analysis. All five DA receptors (D1, D2, D3, D4, and D5) mRNAs and proteins were expressed in MC3T3-E1 cells. DA treatment increased cell proliferation for up to 7 days (P < 0.05). Osteogenic mineralization was significantly greater in the DA-treated group than control group (P < 0.05). Finally, expression of all the osteogenic genes was inhibited by DA receptor antagonists for D1, D3, and D5. Our findings suggest that MC3T3-E1 osteoblasts express functional DA receptors that enhance proliferation and mineralization. PDA is not biologically inert and has important implications in orthopedic applications. Furthermore, osteoblast differentiation might be regulated by the nervous system, presumably during bone development, remodeling, or repair.
Bone formation: Neurotransmitters may boost bone cell division
Brain chemicals called neurotransmitters may play an important role in bone formation, new research from the US suggests. The role of the neurotransmitter dopamine in bone is largely unknown but recent research has suggested that bone cells may respond to neurotransmitters. Dr Ching-Chang Ko from the University of North Carolina and colleagues discovered adding dopamine to bone cells from mice stimulated cell division for up to seven days. Mineralization of the cells, an indication of bone formation, was also greater in the cells treated with dopamine than in untreated cells. The researchers suggest that dopamine can enhance bone regeneration. Using dopamine, potentially in conjunction with bone scaffolds in tissue engineering, could lead to a novel way of growing bone for use in orthopedic applications.
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