title: P2X7 nucleotide receptor plays an important role in callus remodeling during fracture repair.
abstract: The P2X7 nucleotide receptor (P2X7R) is an ATP-gated ion channel expressed in bone cells. Homozygous null P2X7R (P2X7R(-/-)) mice have reduced bone formation, so we hypothesized that P2X7R(-/-) mice have impaired fracture healing compared to P2X7R(+/+) control mice. To test the hypothesis, adult P2X7R(-/-) mice and P2X7R(+/+) mice were studied. Osteotomy of the right femur was performed and a stainless-steel pin was inserted into the medullary cavity to stabilize the fracture site. No differences in callus development were seen in the radiograph, micro computed tomography, or dual-energy x-ray absorptiometry measurements. Mechanical testing showed that the recovery of ultimate force, stiffness, and energy to failure were slightly decreased in P2X7R(-/-) mice compared with the control. Histomorphometric measurements of the callus revealed that mineralizing surface and bone formation were significantly decreased, by 22% (p < 0.001) and 29% (p < 0.05), respectively, in P2X7R(-/-) mice in comparison with the wild-type control. These data show that a null mutation of the P2X7R does not affect the amount of callus formed in our osteotomy fracture model. However, callus remodeling was significantly delayed. Our data suggest the different role of the P2X7R in woven bone and lamellar bone formation.
authors.affiliation: Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA. jilili@iupui.edu
authors.forename: Jiliang
authors.initials: J
authors.lastname: Li
authors.forename: Rachel
authors.initials: R
authors.lastname: Meyer
authors.forename: Randall L
authors.initials: RL
authors.lastname: Duncan
authors.forename: Charles H
authors.initials: CH
authors.lastname: Turner
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000235:genetics*; D016723:Bone Remodeling / Q000235:genetics*; D002146:Bony Callus / Q000378:metabolism / Q000503:physiopathology; D002113:Calcification, Physiologic / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology; D050723:Fractures, Bone / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D020127:Recovery of Function / Q000235:genetics; D013314:Stress, Mechanical; D016474:Weight-Bearing / Q000502:physiology; D014945:Wound Healing / Q000235:genetics
chemical_list: C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7