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

39 Citations (Scopus)

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

Fingerprint

Osteocytes
STAT3 Transcription Factor
Osteoblasts
Osteogenesis
Reactive Oxygen Species
Knockout Mice
Bone Density
Ulna
Spontaneous Fractures
Mutation
Osteoclasts
Mitochondria
Oxidative Stress
Transcription Factors
Bone and Bones

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

Cite this

Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species. / Zhou, Hongkang; Newnum, America B.; Martin, Joseph R.; Li, Ping; Nelson, Mark T.; Moh, Akira; Fu, Xin Yuan; Yokota, Hiroki; Li, Jiliang.

In: Bone, Vol. 49, No. 3, 09.2011, p. 404-411.

Research output: Contribution to journalArticle

Zhou, H, Newnum, AB, Martin, JR, Li, P, Nelson, MT, Moh, A, Fu, XY, Yokota, H & Li, J 2011, 'Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species', Bone, vol. 49, no. 3, pp. 404-411. https://doi.org/10.1016/j.bone.2011.04.020
Zhou, Hongkang ; Newnum, America B. ; Martin, Joseph R. ; Li, Ping ; Nelson, Mark T. ; Moh, Akira ; Fu, Xin Yuan ; Yokota, Hiroki ; Li, Jiliang. / Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species. In: Bone. 2011 ; Vol. 49, No. 3. pp. 404-411.
@article{77ef814d1ab94e86aab5b1dd9d89f883,
title = "Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species",
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.",
keywords = "Bone formation, Mechanotransduction, Mitochondria, Osteoblast, Reactive oxidative stress, Signal transducers and activators of transcription 3",
author = "Hongkang Zhou and Newnum, {America B.} and Martin, {Joseph R.} and Ping Li and Nelson, {Mark T.} and Akira Moh and Fu, {Xin Yuan} and Hiroki Yokota and Jiliang Li",
year = "2011",
month = "9",
doi = "10.1016/j.bone.2011.04.020",
language = "English",
volume = "49",
pages = "404--411",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Osteoblast/osteocyte-specific inactivation of Stat3 decreases load-driven bone formation and accumulates reactive oxygen species

AU - Zhou, Hongkang

AU - Newnum, America B.

AU - Martin, Joseph R.

AU - Li, Ping

AU - Nelson, Mark T.

AU - Moh, Akira

AU - Fu, Xin Yuan

AU - Yokota, Hiroki

AU - Li, Jiliang

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

KW - Bone formation

KW - Mechanotransduction

KW - Mitochondria

KW - Osteoblast

KW - Reactive oxidative stress

KW - Signal transducers and activators of transcription 3

UR - http://www.scopus.com/inward/record.url?scp=79960573429&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960573429&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2011.04.020

DO - 10.1016/j.bone.2011.04.020

M3 - Article

C2 - 21555004

AN - SCOPUS:79960573429

VL - 49

SP - 404

EP - 411

JO - Bone

JF - Bone

SN - 8756-3282

IS - 3

ER -