TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells.

Abstract

Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of the TNF family, is a multifunctional cytokine that regulates cell growth, migration, and survival principally through a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14). However, its physiological roles in bone are largely unknown. We herein report various effects of TWEAK on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed Fn14 and produced RANTES (regulated upon activation, healthy T cell expressed and secreted) upon TWEAK stimulation through PI3K-Akt, but not nuclear factor-kappaB (NF-kappaB), pathway. In addition, TWEAK inhibited bone morphogenetic protein (BMP)-2-induced expression of osteoblast differentiation markers such as alkaline phosphatase through mitogen-activated protein kinase (MAPK) Erk pathway. Furthermore, TWEAK upregulated RANKL (receptor activation of NF-kappaB ligand) expression through MAPK Erk pathway in MC3T3-E1 cells. All these effects of TWEAK on MC3T3-E1 cells were abolished by mouse Fn14-Fc chimera. We also found significant TWEAK mRNA or protein expression in osteoblast- and osteoclast-lineage cell lines or the mouse bone tissue, respectively. Finally, we showed that human osteoblasts expressed Fn14 and induced RANTES and RANKL upon TWEAK stimulation. Collectively, TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in MC3T3-E1 cells. TWEAK may thus be a novel cytokine that regulates several aspects of osteoblast function.

• Authors: Takashi Ando, Jiro Ichikawa, Masanori Wako, Kyosuke Hatsushika, Yoshiyuki Watanabe, Michitomo Sakuma, Kachio Tasaka, Hideoki Ogawa, Yoshiki Hamada, Hideo Yagita, Atsuhito Nakao
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 8 Issue 5 Pg. R146 ( 2006) ISSN: 1478-6362 [Electronic] England
• PMID: 16945157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BMP2 protein, human
• Bmp2 protein, mouse
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins
• Chemokine CCL5
• Cytokine TWEAK
• RANK Ligand
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• Recombinant Proteins
• TNFRSF12A protein, human
• TNFSF11 protein, human
• TWEAK Receptor
• Tnfrsf12a protein, mouse
• Tnfsf11 protein, mouse
• Tnfsf12 protein, mouse
• Transforming Growth Factor beta
• Tumor Necrosis Factors
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• 3T3 Cells
• Animals
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Proteins (pharmacology)
• Cell Differentiation (drug effects)
• Chemokine CCL5 (metabolism)
• Chimera
• Cytokine TWEAK
• Gene Expression (drug effects, physiology)
• Humans
• Mice
• Osteoblasts (cytology, drug effects, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RANK Ligand (genetics)
• RNA, Messenger (metabolism)
• Receptors, Tumor Necrosis Factor (genetics, metabolism)
• Recombinant Proteins (genetics, metabolism, pharmacology)
• Signal Transduction (drug effects, physiology)
• TWEAK Receptor
• Transforming Growth Factor beta (pharmacology)
• Tumor Necrosis Factors (genetics, metabolism, pharmacology)