PI3K activation increases SDF-1 production and number of osteoclast precursors, and enhances SDF-1-mediated osteoclast precursor migration

Naga S Adapala, Sierra Root, Joseph Lorenzo, Hector Aguila, Archana Sanjay

Research output: Contribution to journalArticle

Abstract

Our previous studies showed that in a mouse model in which PI3K-AKT activation was increased (YF mice), osteoclast numbers and levels of SDF-1, a chemokine, were augmented. The purpose of this study was to delineate the role of PI3K activation in regulating SDF-1 production and examine whether SDF-1 can stimulate differentiation and/or migration of osteoclast precursors. Using flow cytometric analysis, we demonstrated that compared to wild type mice, bone marrow of YF mice had increased numbers of CXCL12 abundant reticular (CAR) cells, that are a major cell type responsible for producing SDF-1. At the molecular level, transcription factor specificity protein 1 (Sp1) induced an increased transcription of SDF-1 that was dependent on PI3K/AKT activation. YF mice also contained an increased number of osteoclast precursors, in which expression of CXCR4, a major receptor for SDF-1, was increased. SDF-1 did not induce differentiation of osteoclast precursors into mature osteoclasts; compared to cells derived from WT mice, cells obtained from YF mice were more responsive to SDF-1. In conclusion, we demonstrate that PI3K activation resulted in increased SDF-1, increased the number of osteoclast precursors, and enhanced osteoclast precursor migration in response to SDF-1.

Original languageEnglish (US)
Article number100203
JournalBone Reports
Volume10
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

Keywords

  • CAR cells
  • Migration
  • Osteoclast precursors
  • PI3K
  • SDF-1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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