Sexual differences in bone porosity, osteocyte density, and extracellular matrix organization due to osteoblastic-specific Bmp2 deficiency in mice
Autor: | Sarah McBride-Gagyi, Ashley Ward, Zacharie Toth, Simon Y. Tang |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Toughness medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Bone morphogenetic protein 2 Osteocytes Article Bone and Bones 03 medical and health sciences Mice 0302 clinical medicine Brittleness Internal medicine medicine Animals Porosity Sexual difference Osteoblasts Chemistry Bone fracture medicine.disease Extracellular Matrix 030104 developmental biology medicine.anatomical_structure Endocrinology Osteocyte Female Extracellular matrix organization |
Zdroj: | Bone |
Popis: | Clinical studies have come to conflicting conclusions regarding BMP2 deficiency's link to regulating bone mass and increasing fracture risk. This may be due to the signaling protein having sex- or age-dependent effects. Previous pre-clinical studies have supported a role, but have not adequately determined the physical mechanism causing altered bulk material properties. This study investigated the physical effects of Bmp2 ablation from osteogenic lineage cells (Osx-Cre; Bmp2fl/fl) in 10- and 15-week-old male and female mice. Bones collected post-mortem were subjected to fracture toughness testing, reference point indentation testing, microCT, and histological analysis to determine the multi-scale relationships between mechanical/material behavior and collagen production, collagen organization, and bone architecture. BMP2-deficient bones were smaller, more brittle, and contained more lacunae-scale voids and cortical pores. The cellular density was significantly increased and there were material-level differences measured by reference point indentation, independently of collagen fiber alignment or organization. The disparities in bone size and in bone fracture toughness between genotypes were especially striking in males at 15-weeks-old. Together, this study suggests that there are sex- and age-dependent effects of BMP2 deficiency. The results from both sexes also warrant further investigation into BMP2 deficiency's role in osteoblasts' transition to osteocytes and overall bone porosity. |
Databáze: | OpenAIRE |
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