LIS1 regulates osteoclastogenesis through modulation of M-SCF and RANKL signaling pathways and CDC42

Shiqiao Ye, Toshifumi Fujiwara, Jian Zhou, Kottayil I. Varughese, Haibo Zhao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have previously reported that depletion of LIS1, a key regulator of microtubules and cytoplasmic dynein motor complex, in osteoclast precursor cells by shRNAs attenuates osteoclastogenesis in vitro. However, the underlying mechanisms remain unclear. In this study, we show that conditional deletion of LIS1 in osteoclast progenitors in mice led to increased bone mass and decreased osteoclast number on trabecular bone. In vitro mechanistic studies revealed that loss of LIS1 had little effects on cell cycle progression but accelerated apoptosis of osteoclast precursor cells. Furthermore, deletion of LIS1 prevented prolonged activation of ERK by M-CSF and aberrantly enhanced prolonged JNK activation stimulated by RANKL. Finally, lack of LIS1 abrogated M-CSF and RANKL induced CDC42 activation and retroviral transduction of a constitutively active form of CDC42 partially rescued osteoclastogenesis in LIS1-deficient macrophages. Therefore, these data identify a key role of LIS1 in regulation of cell survival of osteoclast progenitors by modulating M-CSF and RANKL induced signaling pathways and CDC42 activation.

Original languageEnglish
Pages (from-to)1488-1499
Number of pages12
JournalInternational journal of biological sciences
Volume12
Issue number12
DOIs
Publication statusPublished - Nov 25 2016

Fingerprint

osteoclasts
Osteoclasts
Osteogenesis
bone
Macrophage Colony-Stimulating Factor
apoptosis
Cytoplasmic Dyneins
bones
Microtubules
microtubules
cell viability
cell cycle
Cell Survival
Cell Cycle
macrophages
Macrophages
cells
Apoptosis
Bone and Bones
mice

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

LIS1 regulates osteoclastogenesis through modulation of M-SCF and RANKL signaling pathways and CDC42. / Ye, Shiqiao; Fujiwara, Toshifumi; Zhou, Jian; Varughese, Kottayil I.; Zhao, Haibo.

In: International journal of biological sciences, Vol. 12, No. 12, 25.11.2016, p. 1488-1499.

Research output: Contribution to journalArticle

Ye, Shiqiao ; Fujiwara, Toshifumi ; Zhou, Jian ; Varughese, Kottayil I. ; Zhao, Haibo. / LIS1 regulates osteoclastogenesis through modulation of M-SCF and RANKL signaling pathways and CDC42. In: International journal of biological sciences. 2016 ; Vol. 12, No. 12. pp. 1488-1499.
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