Activin A inhibits RANKL-mediated osteoclast formation, movement and function in murine bone marrow macrophage cultures.

Autor:	Fowler TW; Departments of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA gaddydana@uams.edu., Kamalakar A; Departments of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA., Akel NS; Departments of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA., Kurten RC; Departments of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA., Suva LJ; Departments of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA., Gaddy D; Departments of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR 72205 USA gaddydana@uams.edu.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2015 Feb 15; Vol. 128 (4), pp. 683-94. Date of Electronic Publication: 2015 Jan 20.
DOI:	10.1242/jcs.157834
Abstrakt:	The process of osteoclastic bone resorption is complex and regulated at multiple levels. The role of osteoclast (OCL) fusion and motility in bone resorption are unclear, with the movement of OCL on bone largely unexplored. RANKL (also known as TNFSF11) is a potent stimulator of murine osteoclastogenesis, and activin A (ActA) enhances that stimulation in whole bone marrow. ActA treatment does not induce osteoclastogenesis in stroma-free murine bone marrow macrophage cultures (BMM), but rather inhibits RANKL-induced osteoclastogenesis. We hypothesized that ActA and RANKL differentially regulate osteoclastogenesis by modulating OCL precursors and mature OCL migration. Time-lapse video microscopy measured ActA and RANKL effects on BMM and OCL motility and function. ActA completely inhibited RANKL-stimulated OCL motility, differentiation and bone resorption, through a mechanism mediated by ActA-dependent changes in SMAD2, AKT1 and inhibitor of nuclear factor κB (IκB) signaling. The potent and dominant inhibitory effect of ActA was associated with decreased OCL lifespan because ActA significantly increased activated caspase-3 in mature OCL and OCL precursors. Collectively, these data demonstrate a dual action for ActA on murine OCLs. (© 2015. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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