Stat3 in osteocytes mediates osteogenic response to loading

Kylie A. Corry, Hongkang Zhou, Tatiana Brustovetsky, Evan R. Himes, Nicoletta Bivi, M. Ryne Horn, Yukiko Kitase, Joseph M. Wallace, Teresita Bellido, Nikolai Broustovetski, Jiliang Li

Research output: Contribution to journalArticle

Abstract

Signal transducer and activator of transcription 3 (Stat3) is a member of the Stat family of proteins involved in signaling in many different cell types, including osteocytes. Osteocytes are considered major mechanosensing cells in bone due to their intricate dendritic networks able to sense changes in physical force and to orchestrate the response of osteoclasts and osteoblasts. We examined the role of Stat3 in osteocytes by generating mice lacking Stat3 in these cells using the Dmp-1(8kb)-Cre promoter (Stat3cKO mice). Compared to age-matched littermate controls, Stat3cKO mice of either sex (18 weeks old) exhibit reduced bone formation indices, decreased osteoblasts and increased osteoclasts, and altered material properties, without detectable changes in bone mineral density (BMD) or content of either trabecular or cortical bone. In addition, Stat3cKO mice of either sex show significantly decreased load-induced bone formation. Furthermore, pharmacologic inhibition of Stat3 in osteocytes in vitro with WP1066 blocked the increase in cytosolic calcium induced by ATP, a mediator of the cellular responses to sheer stress. WP1066 also increased reactive oxygen species (ROS) production in cultured MLO-Y4 osteocytes. These data demonstrate that Stat3 is a critical mediator of mechanical signals received by osteocytes and suggest that osteocytic Stat3 is a potential therapeutic target to stimulate bone anabolism.

Original languageEnglish (US)
Article number100218
JournalBone Reports
Volume11
DOIs
StatePublished - Dec 1 2019

Fingerprint

Osteocytes
STAT3 Transcription Factor
Osteoclasts
Osteoblasts
Osteogenesis
Bone Density
Bone and Bones
Reactive Oxygen Species
Adenosine Triphosphate
Calcium
Proteins

Keywords

  • ATP
  • Bone formation
  • Mechanotransduction
  • Osteocyte
  • ROS
  • Signal transducers and activators of transcription 3 (Stat3)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Corry, K. A., Zhou, H., Brustovetsky, T., Himes, E. R., Bivi, N., Horn, M. R., ... Li, J. (2019). Stat3 in osteocytes mediates osteogenic response to loading. Bone Reports, 11, [100218]. https://doi.org/10.1016/j.bonr.2019.100218

Stat3 in osteocytes mediates osteogenic response to loading. / Corry, Kylie A.; Zhou, Hongkang; Brustovetsky, Tatiana; Himes, Evan R.; Bivi, Nicoletta; Horn, M. Ryne; Kitase, Yukiko; Wallace, Joseph M.; Bellido, Teresita; Broustovetski, Nikolai; Li, Jiliang.

In: Bone Reports, Vol. 11, 100218, 01.12.2019.

Research output: Contribution to journalArticle

Corry, KA, Zhou, H, Brustovetsky, T, Himes, ER, Bivi, N, Horn, MR, Kitase, Y, Wallace, JM, Bellido, T, Broustovetski, N & Li, J 2019, 'Stat3 in osteocytes mediates osteogenic response to loading', Bone Reports, vol. 11, 100218. https://doi.org/10.1016/j.bonr.2019.100218
Corry KA, Zhou H, Brustovetsky T, Himes ER, Bivi N, Horn MR et al. Stat3 in osteocytes mediates osteogenic response to loading. Bone Reports. 2019 Dec 1;11. 100218. https://doi.org/10.1016/j.bonr.2019.100218
Corry, Kylie A. ; Zhou, Hongkang ; Brustovetsky, Tatiana ; Himes, Evan R. ; Bivi, Nicoletta ; Horn, M. Ryne ; Kitase, Yukiko ; Wallace, Joseph M. ; Bellido, Teresita ; Broustovetski, Nikolai ; Li, Jiliang. / Stat3 in osteocytes mediates osteogenic response to loading. In: Bone Reports. 2019 ; Vol. 11.
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