Open AccessInduction of somatopause in adult mice compromises bone morphology and exacerbates bone loss during aging
Author(s) -
Dixit Manisha,
DuranOrtiz Silvana,
Yildirim Godze,
Poudel Sher Bahadur,
Louis Leeann D.,
Bartke Andrzej,
Schaffler Mitchell B.,
Kopchick John J.,
Yakar Shoshana
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13505
Subject(s) - osteocyte , skeleton (computer programming) , endocrinology , medicine , bone marrow , biology , sclerostin , bone remodeling , senescence , knockout mouse , growth factor , osteoporosis , insulin like growth factor , osteoblast , receptor , anatomy , microbiology and biotechnology , wnt signaling pathway , signal transduction , in vitro , biochemistry
Abstract Somatopause refers to the gradual declines in growth hormone (GH) and insulin‐like growth factor‐1 throughout aging. To define how induced somatopause affects skeletal integrity, we used an inducible GH receptor knockout (iGHRKO) mouse model. Somatopause, induced globally at 6 months of age, resulted in significantly more slender bones in both male and female iGHRKO mice. In males, induced somatopause was associated with progressive expansion of the marrow cavity leading to significant thinning of the cortices, which compromised bone strength. We report progressive declines in osteocyte lacunar number, and increases in lacunar volume, in iGHRKO males, and reductions in lacunar number accompanied by ~20% loss of overall canalicular connectivity in iGHRKO females by 30 months of age. Induced somatopause did not affect mineral/matrix ratio assessed by Raman microspectroscopy. We found significant increases in bone marrow adiposity and high levels of sclerostin, a negative regulator of bone formation in iGHRKO mice. Surprisingly, however, despite compromised bone morphology, osteocyte senescence was reduced in the iGHRKO mice. In this study, we avoided the confounded effects of constitutive deficiency in the GH/IGF‐1 axis on the skeleton during growth, and specifically dissected its effects on the aging skeleton. We show here, for the first time, that induced somatopause compromises bone morphology and the bone marrow environment.