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However, clinical observations have shown that drug or genetic mediated improvement of bone mass might be associated to alterations to bone extracellular matrix (ECM) properties, leading to bone fragility. Hence, in this study we\u00a0propose to characterize the physical, chemical and biomechanical properties of mature bone ECM of germline NPY\u2010Y\n                    <jats:sub>1<\/jats:sub>\n                    R knockout (Y\n                    <jats:sub>1<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, and compare to their wild\u2010type (WT) littermates.\u00a0Our results demonstrated that the high bone mass phenotype observed in Y\n                    <jats:sub>1<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice involves\u00a0alterations in Y\n                    <jats:sub>1<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212\u00a0<\/jats:sup>\n                    bone\u00a0ECM ultrastructure, as a result of accelerated deposition of organic and mineral fractions. In addition, Y\n                    <jats:sub>1<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    bone ECM displays enhanced matrix maturation characterized by greater number of mature\/highly packed collagen fibers without\u00a0pathological accumulation of immature\/mature collagen crosslinks nor compromise of mineral crystallinity. These unique features of Y\n                    <jats:sub>1<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u00a0bone ECM improved the biochemical properties of Y\n                    <jats:sub>1<\/jats:sub>\n                    R\n                    <jats:sup>\u2212\/\u2212\u00a0<\/jats:sup>\n                    bones, reflected by mechanically robust bones with diminished propensity to fracture, contributing to greater bone strength.\u00a0These findings support the future usage of drugs targeting Y\n                    <jats:sub>1<\/jats:sub>\n                    R\u00a0signaling as a promising therapeutic strategy to treat bone loss\u2010related pathologies.\n                  <\/jats:p>","DOI":"10.1096\/fj.201902796r","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:15:58Z","timestamp":1579565758000},"page":"4163-4177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The lack of neuropeptide Y\u2010Y\n                    <sub>1<\/sub>\n                    receptor signaling modulates the chemical and mechanical properties of bone matrix"],"prefix":"10.1096","volume":"34","author":[{"given":"Daniela M.","family":"Sousa","sequence":"first","affiliation":[{"name":"i3S \u2212 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"INEB \u2212 Instituto de Engenharia Biom\u00e9dica, Universidade do Porto Porto Portugal"}]},{"given":"Pedro S.","family":"Martins","sequence":"additional","affiliation":[{"name":"INEGI \u2212 Instituto de Ci\u00eancia e Inova\u00e7\u00e3o em Engenharia Mec\u00e2nica e Engenharia Industrial, Faculdade de Engenharia da Universidade do Porto Porto Portugal"}]},{"given":"Lu\u00eds","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"i3S \u2212 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"INEB \u2212 Instituto de Engenharia Biom\u00e9dica, Universidade do Porto Porto Portugal"},{"name":"ICBAS \u2212 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar Universidade do Porto Porto Portugal"}]},{"given":"Cec\u00edlia J.","family":"Alves","sequence":"additional","affiliation":[{"name":"i3S \u2212 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"INEB \u2212 Instituto de Engenharia Biom\u00e9dica, Universidade do Porto Porto Portugal"}]},{"given":"Maria","family":"Gomez\u2010Lazaro","sequence":"additional","affiliation":[{"name":"i3S \u2212 Instituto de Investiga\u00e7\u00e3o e 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