title: Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors.
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.
authors.affiliation: Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ota
authors.forename: Patrick
authors.initials: P
authors.lastname: Quint
authors.forename: Megan M
authors.initials: MM
authors.lastname: Weivoda
authors.forename: Ming
authors.initials: M
authors.lastname: Ruan
authors.forename: Larry
authors.initials: L
authors.lastname: Pederson
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Westendorf
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Merry Jo
authors.initials: MJ
authors.lastname: Oursler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism* / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D053605:Leukemia Inhibitory Factor; D053773:Transforming Growth Factor beta1
keywords: BSA; CED; CXCL16; Camurati–Englemann disease; Coupling; FBS; IGF-1; LIF; M-CSF; Migration; Osteoclast; PBS; PDGF; QTL; RANKL; S1P; TGF-β; TGF-β1; alpha Minimal Essential Medium; bovine serum albumin; fetal bovine serum; insulin like growth factor 1; leukemia inhibitory factor; macrophage colony stimulating factor; phosphate buffered saline; platelet derived growth factor; quantitative trait locus; receptor activator of NFκB ligand; sphingosine 1 phosphate; transforming growth factor beta 1; αMEM
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