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The lack of neuropeptide Y‐Y 1 receptor signaling modulates the chemical and mechanical properties of bone matrix
Author(s) -
Sousa Daniela M.,
Martins Pedro S.,
Leitão Luís,
Alves Cecília J.,
GomezLazaro Maria,
Neto Estrela,
Conceição Francisco,
Herzog Herbert,
Lamghari Meriem
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902796r
Subject(s) - extracellular matrix , chemistry , microbiology and biotechnology , bone remodeling , phenotype , receptor , bone mineral , osteoporosis , bone healing , neuropeptide y receptor , endocrinology , medicine , neuropeptide , biology , anatomy , biochemistry , gene
Genetic and pharmacological functional studies have provided evidence that the lack of Neuropeptide Y‐Y 1 receptor (Y 1 R) signaling pathway induces a high bone mass phenotype in mice. 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 propose to characterize the physical, chemical and biomechanical properties of mature bone ECM of germline NPY‐Y 1 R knockout (Y 1 R −/− ) mice, and compare to their wild‐type (WT) littermates. Our results demonstrated that the high bone mass phenotype observed in Y 1 R −/− mice involves alterations in Y 1 R −/− bone ECM ultrastructure, as a result of accelerated deposition of organic and mineral fractions. In addition, Y 1 R −/− bone ECM displays enhanced matrix maturation characterized by greater number of mature/highly packed collagen fibers without pathological accumulation of immature/mature collagen crosslinks nor compromise of mineral crystallinity. These unique features of Y 1 R −/− bone ECM improved the biochemical properties of Y 1 R −/− bones, reflected by mechanically robust bones with diminished propensity to fracture, contributing to greater bone strength. These findings support the future usage of drugs targeting Y 1 R signaling as a promising therapeutic strategy to treat bone loss‐related pathologies.