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Mitochondrial Function Is Compromised in Cortical Bone Osteocytes of Long‐Lived Growth Hormone Receptor Null Mice
Author(s) -
Liu Zhongbo,
Solesio Maria E,
Schaffler Mitchell B,
FrikhaBenayed Dorra,
Rosen Clifford J,
Werner Haim,
Kopchick John J,
Pavlov Evgeny V,
Abramov Andrey Y,
Yakar Shoshana
Publication year - 2019
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3573
Subject(s) - endocrinology , osteocyte , medicine , mitochondrion , biology , skeletal muscle , reactive oxygen species , chemistry , microbiology and biotechnology , osteoblast , biochemistry , in vitro
Despite increased longevity and resistance to multiple stressors, growth hormone receptor null (GHRKO) mice exhibit severe skeletal impairment. The role of GHR in maintaining osteocyte mitochondrial function is unknown. We found that GHR ablation was detrimental to osteocyte mitochondrial function. In vivo multiphoton microscopy revealed significant reductions of >10% in mitochondrial membrane potential (MMP) in GHRKO osteocytes and reduced mitochondrial volumetric density. Reductions in MMP were accompanied by reductions in glucose transporter‐1 levels, steady state ATP, NADH redox index, oxygen consumption rate, and mitochondrial reserve capacity in GHRKO osteocytes. Glycolytic capacity did not differ between control and GHRKO males’ osteocytes. However, osteocytes from aged female GHRKO mice exhibited reductions in glycolytic parameters, indicating impairments in glucose metabolism, which may be sex dependent. GHRKO osteocytes exhibited increased levels of cytoplasmic reactive oxygen species (ROS) (both basal and in response to high glucose), insulin‐like growth factor‐1 (IGF‐1), and insulin. Mitochondrial ROS levels were increased and correlated with reduced glutathione in GHRKO osteocytes. Overall, the compromised osteocyte mitochondrial function and responses to metabolic insults strongly correlated with skeletal impairments, suggesting that despite increased life span of the GHRKO mice, skeletal health span is decreased. © 2018 American Society for Bone and Mineral Research.