TSLP is a negative regulator of RANKL-induced osteoclastogenesis.

Abstract

Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family, which is known to activate type 2 innate lymphoid cells, mast cells, and Th2 cells; this activation results in allergic inflammation and host defense against parasites. TSLP has also been shown to promote Th17-mediated immune responses, such as those observed in the development of rheumatoid arthritis; however, its role in osteoclastogenesis remains poorly understood. Here, we investigated the functional involvement of TSLP in RANKL-induced osteoclast differentiation from murine bone marrow-derived macrophages (BMMs). Both RANK- and RANK+ macrophages expressed TSLP receptor (TSLPR), while RANK+ osteoclast precursors maintained TSLPR expression after RANKL stimulation. TSLP stimulation led to inhibition of RANK-induced osteoclast differentiation in wild-type BMMs, but not Tslpr-/- BMMs; TSLP stimulation also led to suppression of osteoclastogenic gene expression (Nfatc1, Acp5, Mmp9, and Ctsk). These inhibitory effects of TSLP were significantly reduced following STAT1 inhibition. Finally, we found that LPS stimulation induced TSLP production in murine calvarial osteoblasts, but not BMMs. Together, these observations suggest that TSLP acts directly on osteoclast precursors to suppress osteoclastogenesis. Osteoblasts, along with other TSLP-producing cells, may therefore contribute to the inhibition of osteoclastogenesis under inflammatory conditions.

• Authors: Tatsukuni Ohno, Takashi Nakamura, Susumu Nakae, Hideaki Morita, Kenji Matsumoto, Hirohisa Saito, Kazuyoshi Takeda, Ko Okumura, Toshifumi Azuma
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 530 Issue 3 Pg. 508-512 (09 24 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32600615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• RANK Ligand
• Tnfsf11 protein, mouse
• Thymic Stromal Lymphopoietin
• TSLP protein, mouse

Topics

• Animals
• Cell Differentiation
• Cells, Cultured
• Cytokines (metabolism)
• Female
• Macrophages (cytology, metabolism)
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Osteoblasts (cytology, metabolism)
• Osteoclasts (cytology, metabolism)
• Osteogenesis
• RANK Ligand (metabolism)
• Thymic Stromal Lymphopoietin