TNF receptor type 1 regulates RANK ligand expression by stromal cells and modulates osteoclastogenesis

Journal of Cellular Biochemistry
Y Abu-AmerTeruhisa Hirayama

Abstract

TNFalpha is a major osteoclastogenic cytokine and a primary mediator of inflammatory osteoclastogenesis. We have previously shown that this cytokine directly targets osteoclasts and their precursors and that deletion of its type-1 receptor (TNFr1) lessens osteoclastogenesis and impacts RANK signaling molecules. Osteoclastogenesis is primarily a RANK/RANKL-dependent event and occurs in an environment governed by both hematopoietic and mesenchymal compartments. Thus, we reasoned that TNF/TNFr1 may regulate RANKL and possibly RANK expression by stromal cells and osteoclast precursors (OCPs), respectively. RT-PCR experiments reveal that levels of RANKL mRNA in WT stromal cells are increased following treatment with 1,25-VD3 compared to low levels in TNFr1-null cells. Expression levels of OPG, the RANKL decoy protein, were largely unchanged, thus supporting a RANKL/OPG positive ratio favoring WT cells. RANK protein expression by OCPs was lower in TNFr1-null cells despite only subtle differences in mRNA expression in both cell types. Mix and match experiments of different cell populations from the two mice phenotypes show that WT stromal cells significantly, but not entirely, restore osteoclastogenesis by TNFr1-null OCPs. Similar res...Continue Reading

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Citations

Nov 8, 2011·Rheumatology International·Shengqian XuJianhua Xu
Sep 2, 2008·Journal of Bone and Mineral Metabolism·Anower Hussain MianKeiichi Ohya
Nov 10, 2005·Journal of Periodontology·P M BartoldD R Haynes
Jul 13, 2006·Annals of the New York Academy of Sciences·Jameel Iqbal
Jun 23, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jennifer KieselRajeev Aurora
Mar 27, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Masashi HonmaHiroshi Suzuki
Oct 13, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yoshiaki KariyaHiroshi Suzuki
Feb 25, 2009·Journal of Biomedical Materials Research. Part a·Nadim James HallabJoshua J Jacobs
Nov 7, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hiroyuki KanzakiToshihisa Kawai
Dec 14, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Benjamin RauwelJean-Luc Davignon
Nov 1, 2005·Journal of Periodontology·P M BartoldD R Haynes
May 20, 2021·Journal of Applied Oral Science : Revista FOB·Ju-Xiang PengJian-Guo Liu

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