Adenosine A2B receptors play an important role in bone homeostasis.
Bone homeostasis is a finely regulated mechanism involving different molecular pathways including adenosine signaling. The aim of this study is to determine the bone phenotype of adenosine A2B receptor knockout (A2BRKO) mice and to measure their ability to form new bone. Moreover, we analyzed the functionality of osteoclasts and osteoblasts from A2BRKO mice. Microcomputed tomography (μCT) analysis revealed a decrease of bone substance, bone mineral density, and trabecular number in A2BRKO mice compared to the WT mice at the same age. We measured the new bone formation by injecting fluorescent markers: it was reduced in femur and tibia of A2BRKO mice compare to the WT. A2BRKO young mice have fewer osteoblasts and an increase of osteoclasts was measured in the hind limbs of young and adult mice. A2BRKO osteoclasts are also more active in vitro, showing an increase of pit formation in dentin discs. Surprisingly in mature osteoblasts from A2BRKO mice, we measured an increase of calcified matrix production, collagen deposition, and alkaline phosphatase activity. These results demonstrate that A2BR on osteoblasts and osteoclasts regulate bone homeostasis.
Division of Translational Medicine, New York, NY, USA. Carmen.Corciulo@nyumc.org.
Carmen
C
Corciulo
Division of Translational Medicine, New York, NY, USA.
Tuere
T
Wilder
Division of Translational Medicine, New York, NY, USA.|Department of Medicine, Division of Rheumatology, NYU School of Medicine, 550 First Ave, New York, NY, 10016, USA.
Bruce N
BN
Cronstein
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D055114:X-Ray Microtomography
D043704:Receptor, Adenosine A2B
A2BRKO mice; Adenosine A2B; Bone homeostasis