S100A12 facilitates osteoclast differentiation from human monocytes.

Abstract

Osteoclasts play a critical role not only in bone homeostasis but also in inflammatory osteolysis, such as that occurring in inflammatory arthritis and systemic inflammation. In both inflammation conditions, inflammatory cytokines like Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α induce RANKL expression in osteoblasts, but the roles of these cytokines in osteoclast activation remain unclear. S100A12, an S100 family member, is a low-molecular-weight calcium-binding protein. Although it has a pro-inflammatory role, its effects on osteoclast differentiation have been unclear. Here we examined the direct effects of S100A12 on human osteoclasts in vitro. S100A12 facilitated osteoclast formation in the presence of RANKL, as judged by the cells' morphology and elevated expression of osteoclast-related molecules, including NFATc1, ACP5, CALCR, and ITGβ3. In addition, S100A12 administration markedly enhanced the osteoclasts' bone resorption ability, consistent with their increased expression levels of CTSK and CA2. Blocking RAGE and TLR4 cancelled the effects of S100A12. Our results indicate that S100A12 is a potential therapeutic target for inflammatory osteolysis.

• Authors: Miwa Nishida, Jun Saegusa, Shino Tanaka, Akio Morinobu
• Journal: PloS one (PLoS One) Vol. 13 Issue 9 Pg. e0204140 ( 2018) ISSN: 1932-6203 [Electronic] United States
• PMID: 30235276 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• Biomarkers
• Lipopolysaccharide Receptors
• S100A12 Protein
• Toll-Like Receptor 4
• MOK protein, human
• Mitogen-Activated Protein Kinases

Topics

• Antigens, Neoplasm (metabolism)
• Biomarkers (metabolism)
• Bone Resorption (metabolism, pathology)
• Cell Differentiation
• Humans
• Lipopolysaccharide Receptors (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Monocytes (metabolism)
• Osteoclasts (cytology, metabolism)
• S100A12 Protein (metabolism)
• Toll-Like Receptor 4 (metabolism)