beta2- and beta3-, but not beta1-adrenergic receptors are involved in osteogenesis of mouse mesenchymal stem cells via cAMP/PKA signaling.

The osteogenic capacity of mesenchymal stem cells (MSCs) and the importance of beta-adrenergic signals in bone formation and resorption have been well investigated. However, little is known about the development of beta-adrenergic receptor (beta-AR) systems and the role of beta-adrenergic signals in osteogenic differentiation of MSCs, which is critically important in bone physiology and pharmacology. In this study, we demonstrated that both the mRNA and protein levels of beta2- and beta3-AR are up-regulated following osteogenesis of mouse MSCs. We also established that beta-AR agonists negatively while antagonists positively affect MSC osteogenesis. Both beta2- and beta3-AR are involved in MSC osteogenesis, with beta2-AR being dominant. The effect of beta-ARs on MSC osteogenesis is partly mediated via the cAMP/PKA signaling. These findings suggest that MSC is also a target for beta-adrenergic regulation and beta-adrenergic signaling plays a role in MSC osteogenesis.