BoneKEy Reports | BoneKEy Watch
A2BAR and cAMP signaling direct osteoblast differentiation
DOI:10.1038/bonekey.2012.84
The A2B adenosine receptor, A2BAR, is a Gαs/αq-protein-coupled receptor that is known to be activated by the small increases in extracellular ATP that occur in response to bone injury. In this study, the role of A2BAR in the differentiation pathway by which mesenchymal stem cells (MSCs) develop into osteoblasts was studied using A2BAR knockout (KO) mice.
In vitro experiments showed that the A2BAR KO mice showed a reduction in osteoblast differentiation from MSCs. Increasing the expression of A2BAR also increased the level of key transcription factors produced by active osteoblasts, and resulted in an increased number of osteoblasts in culture.
The investigation then switched to the in vivo effects of A2BAR; the A2BAR KO mice showed clearly impaired bone healing after experimental fracture, probably due to the impaired differentiation of MSCs into osteoblasts. The KO mice also showed a lower bone volume and reduced bone mineral density at 15 weeks old, compared with wild type mice, indicating that they have an osteopenic phenotype.
Editor's comment: It has long been known that cAMP is important in osteoblast biology. This novel study identifies A2BAR as a regulator of bone homeostasis and an important component of fracture healing, through its effects on osteoblast differentiation.
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