title: Aberrant bone density in aging mice lacking the adenosine transporter ENT1.
abstract: Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America ; Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hinton
authors.affiliation: Department of Orthopedic Surgery and Orthopedic Research, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: McGee-Lawrence
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Moonnoh R
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Advanced Genomics Technology Center, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Hoi K
authors.initials: HK
authors.lastname: Kwong
authors.affiliation: Department of Orthopedic Surgery and Orthopedic Research, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America ; Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America ; Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D015519:Bone Density / Q000235:genetics* / Q000502:physiology*; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics*; D005269:Femur / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D008159:Lumbar Vertebrae / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009929:Organ Size / Q000235:genetics / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D045442:Rotarod Performance Test
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D012333:RNA, Messenger; C498476:SLC29A1 protein, mouse