title: Neuropeptide Y modulates fracture healing through Y1 receptor signaling.
abstract: Neuropeptide Y acting via it's Y1 receptor represents a powerful pathway in the control of bone mass. The global or osteoblast-specific Y1 receptor deletion induces pronounced bone anabolic effects in mice. However, the contribution of Y1 receptor deletion in bone repair/healing remained to be clarified. Therefore, in this study we characterized the role of Y1 receptor deletion in fracture healing. Closed tibial fractures were generated in germline (Y1 (-/-) ) and osteoblastic-specific Y1 receptor knockout mice. The progression of tibial repair monitored from 1- until 6-weeks post-fracture demonstrated that in Y1 (-/-) mice there is a delay in fracture repair, as seen by a decrease in bone callus volume and callus strength. Moreover, the histological features included elevated avascular and cartilage area and consequently delayed cartilage removal, and hence impaired union. Interestingly, this delay in bone repair was not related directly to Y1 receptors expressed by mature osteoblasts. These findings suggest that the global absence of the Y1 receptor delays fracture healing, through impairing the early phases of fracture repair to achieve bony union. The data acquired on the role of Y1 receptor signaling disruption in bone regeneration is critical for the design of future therapeutic strategies.
authors.affiliation: Instituto de Engenharia Biomédica (INEB), NEWTherapies Group, Universidade do Porto, Porto, Portugal.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Sousa
authors.forename: Michelle M
authors.initials: MM
authors.lastname: McDonald
authors.forename: Kathy
authors.initials: K
authors.lastname: Mikulec
authors.forename: Lauren
authors.initials: L
authors.lastname: Peacock
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: Meriem
authors.initials: M
authors.lastname: Lamghari
authors.forename: David G
authors.initials: DG
authors.lastname: Little
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor
keywords: Y1 receptor; bone; fracture healing; nervous system; neuropeptide Y