Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species

Hongkang Zhou, America B. Newnum, Joseph R. Martin, Ping Li, Mark T. Nelson, Akira Moh, Xin Yuan Fu, Hiroki Yokota, Jiliang Li

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Signal transducers and activators of transcription 3 (Stat3) is a transcription factor expressed in many cell types including osteoblasts, osteocytes, and osteoclasts. STAT3 mutations cause a rare human immunodeficiency disease that presents reduced bone mineral density and recurrent pathological fractures. To investigate the role of Stat3 in load-driven bone metabolism, two strains of osteoblast/osteocyte-selective Stat3 knockout (KO) mice were generated. Compared to age-matched littermate controls, this selective inactivation of Stat3 significantly lowered bone mineral density (7-12%, p. < 0.05) as well as ultimate force (21-34%, p. < 0.01). In ulna loading (2.50-2.75. N with 120 cycles/day at 2. Hz for 3 consecutive days), Stat3 KO mice were less responsive than littermate controls as indicated by reduction in relative mineralizing surface (rMS/BS, 47-59%, p. < 0.05) and relative bone formation rate (rBFR/BS, 64-75%, p. < 0.001). Furthermore, inactivation of Stat3 suppressed load-driven mitochondrial activity, which led to an elevated level of reactive oxygen species (ROS) in cultured primary osteoblasts. Taken together, the results support the notion that the loss-of-function mutation of Stat3 in osteoblasts and osteocytes diminishes load-driven bone formation and impairs the regulation of oxidative stress in mitochondria.

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalBone
Volume49
Issue number3
DOIs
StatePublished - Sep 1 2011

Keywords

  • Bone formation
  • Mechanotransduction
  • Mitochondria
  • Osteoblast
  • Reactive oxidative stress
  • Signal transducers and activators of transcription 3

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

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    Zhou, H., Newnum, A. B., Martin, J. R., Li, P., Nelson, M. T., Moh, A., Fu, X. Y., Yokota, H., & Li, J. (2011). Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species. Bone, 49(3), 404-411. https://doi.org/10.1016/j.bone.2011.04.020