Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors

Kuniaki Ota, Patrick Quint, Megan M. Weivoda, Ming Ruan, Larry Pederson, Jennifer J. Westendorf, Sundeep Khosla, Merry Jo Oursler

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

The processes of bone resorption and bone formation are tightly coupled in young adults, which is crucial to maintenance of bone integrity. We have documented that osteoclasts secrete chemotactic agents to recruit osteoblast lineage cells, contributing to coupling. Bone formation subsequent to bone resorption becomes uncoupled with aging, resulting in significant bone loss. During bone resorption, osteoclasts release and activate transforming growth factor beta 1 (TGF-β1) from the bone matrix; thus, elevated bone resorption increases the level of active TGF-β in the local environment during aging. In this study, we examined the influences of TGF-β1 on the ability of osteoclasts to recruit osteoblasts. TGF-β1 increased osteoclast expression of the chemokine CXCL16 to promote osteoblast migration. TGF-β1 also directly stimulated osteoblast migration; however, this direct response was blocked by conditioned medium from TGF-β1-treated osteoclasts due to the presence of leukemia inhibitory factor (LIF) in the medium. CXCL16 and LIF expression was dependent on TGF-β1 activation of Smad2 and Smad3. These results establish that TGF-β1 induces CXCL16 and LIF production in osteoclasts, which modulate recruitment of osteoblasts to restore the bone lost during the resorptive phase of bone turnover.

Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalBone
Volume57
Issue number1
DOIs
Publication statusPublished - 2013 Nov

Keywords

  • CXCL16
  • Coupling
  • LIF
  • Migration
  • Osteoclast
  • TGF-β

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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