IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

Abstract

Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption.

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review

“…IL-1 increases bone resorption by upregulating both differentiation and activation of osteoclasts as well as by stimulating the release of degradative products, such as matrix metalloproteinases [82].…”

Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

“…After 5 days, formation of pits was evaluated. Data are expressed as resorption pits area per total surface area as described previously [ 40 ].…”

“…Each reaction consisted of 2 μL cDNA, a 23 μL mixture of SYBR Premix Ex Taq (Takara, Shiga, Japan), and 50 pmol/μL primers. PCR cycling conditions were as follows: initial denaturation stage (95 °C for 30 s), amplification stage (50 amplification cycles of a denaturation step of 95 °C for 5 s and an annealing step of 60 °C for 30 s), and a final dissociation stage (95 °C for 15 s, 60 °C for 30 s, and 95 °C for 15 s) as previously reported [ 40 ]. The primers used are listed in Table 1 .…”

IL-1R2 Polymorphisms and its Interaction Associates With Osteoporosis Susceptibility in Chinese Han Population

“…Interleukins (ILs), a group of cytokines, are reported to be related to the development of osteoporosis, which is characterized by an imbalance between bone formation and bone resorption [11,12]. IL-1 can upregulate the differentiation and activation of osteoclasts and motivate the release of degradative products, thereby increasing bone resorption [13]. Moreover, IL-1 induces the occurrence and development of osteoporosis by interacting synergistically with other cytokines, including, IL-6, IL-31, and TNF [14].…”