Inhibition of osteoclastogenesis by interleukin‐33 administration in the periodontal ligament under mechanical loading
Journal of Periodontal Research(2022)
摘要
Background and objectives The molecular mechanisms mediating external root resorption are poorly understood. Interleukin-33 (IL-33) expression increased remarkably in the periodontal ligament (PDL) under orthodontic loading. The IL-33-driven responses are delicately cell type- and tissue context-dependent. It is unknown how IL-33 act on osteoclastogenesis in the context of root surface. This study aimed to investigate the effect of IL-33 on osteoclastogenesis in the PDL under mechanical loading. Materials and Methods C57BL/6J mice were treated with injections of phosphate buffer saline (PBS) or recombinant mouse IL-33 (rmIL-33, 6 mu l, 30 mu g/ml), and subjected to models of orthodontic tooth movement. Tartrated resistant acid phosphates (TRAP)-positive cells and IL-33 expressions were examined in the PDL. IL-33 release from human PDL cells (hPDLCs) was detected by ELISA. Cementoblast-like (OCCM-30) cells were cultured in the presence of rmIL-33 to examine the release of osteoclast-regulatory proteins. The effects of rmIL-33 on osteoclastogenesis were examined in vitro in cultures of bone marrow macrophages (BMMs) and in BMMs-OCCM-30 cocultures. Expressions of osteoclast-specific or -related genes and proteins were investigated in BMMs-OCCM-30 cocultures treated with or without rmIL-33, in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody. Results Interleukin-33 expressions were upregulated in the PDL under orthodontic loading. Static compressive force enhanced expression and release of IL-33 from hPDLCs. Administration of rmIL-33 resulted in reduced number of TRAP-positive cells in the PDL, and inhibited osteoclast differentiation from BMMs in vitro. OCCM-30 cells had varied osteoprotegerin (OPG) / receptor activator for nuclear factor-kappa B ligand (RANKL) secretion and increased release of GM-CSF under rmIL-33 stimulation. Treatment with rmIL-33 in BMMs-OCCM-30 cocultures resulted in inhibited differentiation and decreased activity of osteoclasts, and these effects were partially reversed by GM-CSF neutralizing antibody. Conclusions Interleukin-33 inhibits osteoclastogenesis in the PDL under orthodontic loading. The anti-osteoclastogenic effects were mediated partly by directly affecting osteoclast precursors and partly by cementoblast-mediated release of GM-CSF.
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关键词
cementoblasts, GM-CSF, Interleukin-33, osteoclasts
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