Stimulation by toll-like receptors inhibits osteoclast differentiation.
Reads0
Chats0
TLDR
This article showed that TLR stimulation of osteoclast precursors by these microbial products strongly inhibited their differentiation into multinucleated, mature osteoclasts induced by TNF-related activation-induced cytokine.Abstract:
Osteoclasts, the cells capable of resorbing bone, are derived from hemopoietic precursor cells of monocyte-macrophage lineage. The same precursor cells can also give rise to macrophages and dendritic cells, which are essential for proper immune responses to various pathogens. Immune responses to microbial pathogens are often triggered because various microbial components induce the maturation and activation of immunoregulatory cells such as macrophages or dendritic cells by stimulating Toll-like receptors (TLRs). Since osteoclasts arise from the same precursors as macrophages, we tested whether TLRs play any role during osteoclast differentiation. We showed here that osteoclast precursors prepared from mouse bone marrow cells expressed all known murine TLRs (TLR1-TLR9). Moreover, various TLR ligands (e.g., peptidoglycan, poly(I:C) dsRNA, LPS, and CpG motif of unmethylated DNA, which act as ligands for TLR2, 3, 4, and 9, respectively) induced NF-kappa B activation and up-regulated TNF-alpha production in osteoclast precursor cells. Unexpectedly, however, TLR stimulation of osteoclast precursors by these microbial products strongly inhibited their differentiation into multinucleated, mature osteoclasts induced by TNF-related activation-induced cytokine. Rather, TLR stimulation maintained the phagocytic activity of osteoclast precursors in the presence of osteoclastogenic stimuli M-CSF and TNF-related activation-induced cytokine. Taken together, these results suggest that TLR stimulation of osteoclast precursors inhibits their differentiation into noninflammatory mature osteoclasts during microbial infection. This process favors immune responses and may be critical to prevent pathogenic effects of microbial invasion on bone.read more
Citations
More filters
Journal ArticleDOI
OSTEOIMMUNOLOGY: Interplay Between the Immune System and Bone Metabolism
Matthew C. Walsh,Nacksung Kim,Yuho Kadono,Jaerang Rho,Soo Young Lee,Joseph A. Lorenzo,Yongwon Choi +6 more
TL;DR: Bone and the immune system have converged in recent years under the banner of osteo-immunology as mentioned in this paper under the name of bone and immune system, and various factors produced during immune responses are capable of profoundly affecting regulation of bone.
Osteoimmunology: Interplay Between the Immune System and Bone
Matthew C. Walsh,Nacksung Kim,Yuho Kadono,Jaerang Rho,Soo-Young Lee,Joseph A. Lorenzo,Yongwon Choi +6 more
TL;DR: Efforts are currently under way to further characterize how these two organ systems overlap and to develop therapeutic strategies that benefit from this understanding.
Journal ArticleDOI
Osteoimmunology: interactions of the bone and immune system.
TL;DR: This review is meant to provide a broad overview of the many ways that bone and immune cells interact so that a better understanding of the role that each plays in the development and function of the other can develop.
Journal ArticleDOI
Tumor necrosis factor receptor‐ associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system
TL;DR: Tumor necrosis factor receptor (TNFR)‐associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein–protein interactions via its TRAF domain and a RING finger domain that possesses non‐conventional E3 ubiquitin ligase activity.
References
More filters
Journal ArticleDOI
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,Christophe Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Silva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,Betsy Layton,Bruce Beutler +13 more
TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
Journal ArticleDOI
A Toll-like receptor recognizes bacterial DNA.
Hiroaki Hemmi,Osamu Takeuchi,Taro Kawai,Tsuneyasu Kaisho,Shintaro Sato,Hideki Sanjo,Makoto Matsumoto,Katsuaki Hoshino,Hermann Wagner,Kiyoshi Takeda,Shizuo Akira +10 more
TL;DR: It is shown that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9, and vertebrate immune systems appear to have evolved a specific Toll- like receptor that distinguishes bacterial DNA from self-DNA.
Journal ArticleDOI
Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.
TL;DR: It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).
Journal ArticleDOI
The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5.
Fumitaka Hayashi,Kelly D. Smith,Adrian Ozinsky,Thomas R. Hawn,Thomas R. Hawn,Eugene C. Yi,David R. Goodlett,Jimmy K. Eng,Shizuo Akira,David M. Underhill,Alan Aderem +10 more
TL;DR: It is reported that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production, and the data suggest thatTLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flageLLated bacterial pathogens.
Journal ArticleDOI
Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families.
TL;DR: Osteoblasts/stromal cells can now be replaced with RANKL and M-CSF in dealing with the whole life of osteoclasts, and new ways to treat several metabolic bone diseases caused by abnormal osteoclast recruitment and functions will be established.
Related Papers (5)
Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation
David L. Lacey,Emma Timms,Hong-Lin Tan,Michael J. Kelley,Colin R. Dunstan,Tim Burgess,Robin Elliott,Anne Colombero,Gary Elliott,S. Scully,Hailing Hsu,John K. Sullivan,Nessa Hawkins,E. Davy,C. Capparelli,Alana Eli,Yi-xin Qian,Steve Kaufman,Ildiko Sarosi,Victoria Shalhoub,Giorgio Senaldi,Jane Guo,John M. Delaney,William J. Boyle +23 more