PMID- 37418415
OWN - NLM
STAT- MEDLINE
DCOM- 20230710
LR  - 20231124
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 7
DP  - 2023
TI  - Increased tissue modulus and hardness in the TallyHO mouse model of early onset 
      type 2 diabetes mellitus.
PG  - e0287825
LID - 10.1371/journal.pone.0287825 [doi]
LID - e0287825
AB  - Individuals with type 2 diabetes mellitus (T2DM) have a higher fracture risk 
      compared to those without T2DM despite having higher bone mineral density (BMD). 
      Thus, T2DM may alter other aspects of resistance to fracture beyond BMD such as 
      bone geometry, microarchitecture, and tissue material properties. We 
      characterized the skeletal phenotype and assessed the effects of hyperglycemia on 
      bone tissue mechanical and compositional properties in the TallyHO mouse model of 
      early-onset T2DM using nanoindentation and Raman spectroscopy. Femurs and tibias 
      were harvested from male TallyHO and C57Bl/6J mice at 26 weeks of age. The 
      minimum moment of inertia assessed by micro-computed tomography was smaller 
      (-26%) and cortical porosity was greater (+490%) in TallyHO femora compared to 
      controls. In three-point bending tests to failure, the femoral ultimate moment 
      and stiffness did not differ but post-yield displacement was lower (-35%) in the 
      TallyHO mice relative to that in C57Bl/6J age-matched controls after adjusting 
      for body mass. The cortical bone in the tibia of TallyHO mice was stiffer and 
      harder, as indicated by greater mean tissue nanoindentation modulus (+22%) and 
      hardness (+22%) compared to controls. Raman spectroscopic mineral:matrix ratio 
      and crystallinity were greater in TallyHO tibiae than in C57Bl/6J tibiae 
      (mineral:matrix +10%, p < 0.05; crystallinity +0.41%, p < 0.10). Our regression 
      model indicated that greater values of crystallinity and collagen maturity were 
      associated with reduced ductility observed in the femora of the TallyHO mice. The 
      maintenance of structural stiffness and strength of TallyHO mouse femora despite 
      reduced geometric resistance to bending could potentially be explained by 
      increased tissue modulus and hardness, as observed at the tibia. Finally, with 
      worsening glycemic control, tissue hardness and crystallinity increased, and bone 
      ductility decreased in TallyHO mice. Our study suggests that these material 
      factors may be sentinels of bone embrittlement in adolescents with T2DM.
CI  - Copyright: (c) 2023 Arora et al. This is an open access article distributed under 
      the terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Arora, Daksh
AU  - Arora D
AUID- ORCID: 0000-0002-1707-2284
AD  - Department of Materials Science and Engineering, Cornell University, Ithaca, New 
      York, United States of America.
FAU - Taylor, Erik A
AU  - Taylor EA
AD  - Sibley School of Mechanical and Aerospace Engineering, Cornell University, 
      Ithaca, New York, United States of America.
FAU - King, Karen B
AU  - King KB
AD  - Department of Orthopedics, University of Colorado School of Medicine, Aurora, 
      Colorado, United States of America.
FAU - Donnelly, Eve
AU  - Donnelly E
AUID- ORCID: 0000-0001-8165-9568
AD  - Department of Materials Science and Engineering, Cornell University, Ithaca, New 
      York, United States of America.
AD  - Research Institute, Hospital for Special Surgery, New York, New York, United 
      States of America.
LA  - eng
GR  - K01 AR064314/AR/NIAMS NIH HHS/United States
GR  - P30 DK020595/DK/NIDDK NIH HHS/United States
GR  - P30 DK057516/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230707
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Mice
MH  - Male
MH  - Animals
MH  - Bone Density/genetics
MH  - *Diabetes Mellitus, Type 2
MH  - X-Ray Microtomography
MH  - Hardness
MH  - *Fractures, Bone
MH  - Mice, Inbred C57BL
MH  - Disease Models, Animal
PMC - PMC10328374
COIS- All authors declare that they have no conflict of interest or disclosures.
EDAT- 2023/07/07 19:13
MHDA- 2023/07/10 06:42
PMCR- 2023/07/07
CRDT- 2023/07/07 13:35
PHST- 2022/08/31 00:00 [received]
PHST- 2023/06/14 00:00 [accepted]
PHST- 2023/07/10 06:42 [medline]
PHST- 2023/07/07 19:13 [pubmed]
PHST- 2023/07/07 13:35 [entrez]
PHST- 2023/07/07 00:00 [pmc-release]
AID - PONE-D-22-16499 [pii]
AID - 10.1371/journal.pone.0287825 [doi]
PST - epublish
SO  - PLoS One. 2023 Jul 7;18(7):e0287825. doi: 10.1371/journal.pone.0287825. 
      eCollection 2023.