Adenosine and bone metabolism

Abstract

Bone is a dynamic organ that undergoes continuous remodeling whilst maintaining a balance between bone formation and resorption. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, the cells that resorb bone, act in concert to maintain bone homeostasis. In recent years, there has been increasing appreciation of purinergic regulation of bone metabolism. Adenosine, released locally, mediates its physiologic and pharmacologic actions via interactions with G-protein coupled receptors and recent work has indicated that these receptors are involved in the regulation of osteoclast differentiation and function, as well as osteoblast differentiation and bone formation. Moreover, adenosine receptors also regulate chondrocyte and cartilage homeostasis. These recent findings underscore the potential therapeutic importance of adenosine receptors in regulating bone physiology and pathology.

Direct or indirect stimulation of adenosine A 2A receptors enhances bone regeneration as well as bone morphogenetic protein‐2

“…Here we describe, for the first time, a direct effect of A2AR activation on bone regeneration in vivo, either via direct activation of the receptor or by enhancing extracellular adenosine levels by blockade of Ent1 transporter. Previously, we reported that activation of the A2AR inhibits osteoclast differentiation (17)(18)(19) both in vitro and . Immunohistochemistry for markers of bone remodeling.…”

Regulation of bone and cartilage by adenosine signaling

“…Repair of the skeletal system depends on the differentiation of osteoblasts from their progenitors (mesenchymal stem cells, MSCs) which have a broad, multilineage differentiation potential and express A1, A2A, A2B, and A3 receptors [67,68] (see Fig. 3).…”

A2B Adenosine Receptor Stimulation Down-regulates M-CSF-mediated Osteoclast Proliferation

“…When bones are damaged, increased extracellular ATP produces adenosine, a purine nucleoside produced in response to low-oxygen and inflammatory stimuli (Mediero and Cronstein, 2013;Bowler et al, 2001;Orriss et al, 2010).…”

“…Adenosine binds to four adenosine receptors (A1R, A2AR, A2BAR and A3R) that are members of the G proteincoupled receptor family for the specific actions (Mediero and Cronstein, 2013;Bowler et al, 2001;Orriss et al, 2010).…”

“…Stimulation of A2AR, A2BAR and A3R inhibits osteoclast differentiation and function, whereas A1R stimulates it (Mediero and Cronstein, 2013;Orriss et al, 2010;Ham and Evans, 2012;Kara et al, 2010). A2BAR stimulation by its specific agonist BAY 60-6583 promotes osteoblast differentiation through modulation of Runx2 and Osterix levels and decreases osteoclast differentiation (Corciulo et al, 2016;Carroll et al, 2012;Trincavelli et al, 2014).…”