Browsing by Author "Vasconcelos, Daniel M."
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- Bone injury and repair trigger central and peripheral NPY Neuronal PathwaysPublication . Alves, Cecília J.; Alencastre, Inês S.; Neto, Estrela; Ribas, João; Ferreira, Sofia; Vasconcelos, Daniel M.; Sousa, Daniela M.; Summavielle, Teresa; Lamghari, MeriemBone repair is a specialized type of wound repair controlled by complex multi-factorial events. The nervous system is recognized as one of the key regulators of bone mass, thereby suggesting a role for neuronal pathways in bone homeostasis. However, in the context of bone injury and repair, little is known on the interplay between the nervous system and bone. Here, we addressed the neuropeptide Y (NPY) neuronal arm during the initial stages of bone repair encompassing the inflammatory response and ossification phases in femoral-defect mouse model. Spatial and temporal analysis of transcriptional and protein levels of NPY and its receptors, Y1R and Y2R, reported to be involved in bone homeostasis, was performed in bone, dorsal root ganglia (DRG) and hypothalamus after femoral injury. The results showed that NPY system activity is increased in a time- and space-dependent manner during bone repair. Y1R expression was trigged in both bone and DRG throughout the inflammatory phase, while a Y2R response was restricted to the hypothalamus and at a later stage, during the ossification step. Our results provide new insights into the involvement of NPY neuronal pathways in bone repair.
- Fibrinogen scaffolds with immunomodulatory properties promote in vivo bone regenerationPublication . Vasconcelos, Daniel M.; Gonçalves, Raquel M.; Almeida, Catarina R.; Pereira, Inês O.; Oliveira, Marta I.; Neves, Nuno; Silva, Andreia M.; Ribeiro, António C.; Cunha, Carla; Almeida, Ana R.; Ribeiro, Cristina C.; Gil, Ana M.; Seebach, Elisabeth; Kynast, Katharina L.; Richter, Wiltrud; Lamghari, Meriem; Santos, Susana G.; Barbosa, Mário A.The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at two important time points, addressing the bone regenerative process and the local and systemic immune responses, both crucial to elucidate the mechanisms of tissue remodelling. Fg-3D led to early infiltration of granulation tissue (6 days post-implantation), followed by bone defect closure, including periosteum repair (8 weeks post-injury). In the acute inflammatory phase (6 days) local gene expression analysis revealed significant increases of pro-inflammatory cytokines IL-6 and IL-8, when compared with non-operated animals. This correlated with modified proportions of systemic immune cell populations, namely increased T cells and decreased B, NK and NKT lymphocytes and myeloid cell, including the Mac- 1þ (CD18þ/CD11bþ) subpopulation. At 8 weeks, Fg-3D led to decreased plasma levels of IL-1b and increased TGF-b1. Thus, our data supports the hypothesis, establishing a link between bone repair induced by Fg-3D and the immune response. In this sense, Fg-3D scaffolds may be considered immunomodulatory biomaterials.