Instituto de Engenharia Biomédica (INEB), NEWTherapies Group, Universidade do Porto, Porto, Portugal.
J Orthop Res. 2013 Oct;31(10):1570-8. doi: 10.1002/jor.22400. Epub 2013 Jun 3.
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.
神经肽 Y 通过其 Y1 受体发挥作用，代表了控制骨量的强大途径。全球或成骨细胞特异性 Y1 受体缺失可诱导小鼠明显的骨合成代谢效应。然而，Y1 受体缺失在骨修复/愈合中的作用仍有待阐明。因此，在这项研究中，我们研究了 Y1 受体缺失在骨折愈合中的作用。在种系（Y1（-/-））和成骨细胞特异性 Y1 受体敲除小鼠中生成闭合性胫骨骨折。从骨折后 1 周到 6 周监测胫骨修复的进展表明，在 Y1（-/-）小鼠中，骨折修复延迟，表现为骨痂体积和骨痂强度减少。此外，组织学特征包括无血管和软骨区域增加，从而导致软骨去除延迟，进而影响愈合。有趣的是，这种骨修复延迟与成熟成骨细胞表达的 Y1 受体无关。这些发现表明，Y1 受体的缺失会延迟骨折愈合，通过损害骨折修复的早期阶段来实现骨愈合。获得的关于 Y1 受体信号转导中断在骨再生中的作用的数据对于未来治疗策略的设计至关重要。
