TY - JOUR
T1 - Sexual differences in bone porosity, osteocyte density, and extracellular matrix organization due to osteoblastic-specific Bmp2 deficiency in mice
AU - Toth, Zacharie
AU - Ward, Ashley
AU - Tang, Simon Y.
AU - McBride-Gagyi, Sarah
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - BMP2
KW - Bone quality
KW - Bone uCT
KW - Genetic animal models
KW - Histology
UR - http://www.scopus.com/inward/record.url?scp=85106249084&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2021.116002
DO - 10.1016/j.bone.2021.116002
M3 - Article
C2 - 33971313
AN - SCOPUS:85106249084
SN - 8756-3282
VL - 150
JO - Bone
JF - Bone
M1 - 116002
ER -