Abstract
Chronic apical periodontitis is characterized by alveolar bone absorption in the apical region and is the result of the participation of various inflammatory mediators. Studies have shown that the Bruton tyrosine kinase- (Btk-) phospholipase Cγ2 (PLCγ2) signaling pathway plays an important role in bone absorption, but it is unknown whether it plays a role in apical periodontitis bone destruction. Therefore, this study verified the role of Btk and PLCγ2 in bone resorption of apical periodontitis by in vivo and in vitro experiments. In the in vivo experiment, a mice model of apical periodontitis was established; apical bone resorption was confirmed by the numbers of osteoclasts and HE staining. Btk, PLCγ2, and nuclear factor of activated T-cells 1 (NFATc-1) were detected by immunohistochemical staining. In the in vitro experiment, lipopolysaccharides (LPS) were used to stimulate osteoclast precursor cell RAW264.7 to establish an inflammatory microenvironment and detect osteoclast differentiation. By silencing Btk, the expression of Btk, PLCγ2, and NFATc-1 was detected by real-time qPCR and Western blot, and osteoclastogenesis was detected by enzyme histochemical staining to further confirm the role of Btk in bone resorption. It was found that the expression of Btk, PLCγ2, and NFATc-1 changed significantly with the progression of inflammation and bone destruction, indicating that Btk and PLCγ2 may be involved in the progression of inflammation in apical periodontitis and bone absorption. In vitro experiments confirmed that the differentiation of osteoclasts and the expression of PLCγ2 and NFATc-1 were significantly inhibited after silencing Btk expression, but osteoclast precursor cells could be differentiated due to the proinflammatory factor lipopolysaccharide. This study demonstrates that Btk and PLCγ2 are key factors involved in the apical inflammatory response and bone destruction.
Highlights
Chronic apical periodontitis is caused by polymicrobial infection, such as bacterial, viral, and fungal [1], and alveolar bone resorption in the apical region is the main characteristic, which is the result of the participation of multiple inflammatory mediators [2]
The expression of phospholipase Cγ2 (PLCγ2) increased with increased inflammatory cell infiltration and alveolar bone resorption (Figure 2(a))
The results of this study indicate that Bruton tyrosine kinase (Btk) enhanced the differentiation of osteoclasts in an inflammatory environment, which was mainly achieved by regulating the expression of PLCγ2 and nuclear factor of activated T-cells 1 (NFATc-1)
Summary
Chronic apical periodontitis is caused by polymicrobial infection, such as bacterial, viral, and fungal [1], and alveolar bone resorption in the apical region is the main characteristic, which is the result of the participation of multiple inflammatory mediators [2]. Bruton tyrosine kinase (Btk) is a member of the nonreceptor Tec tyrosine kinase family, and these kinases are predominantly expressed in lymphocytes and myeloid cells [3]. When the nonreceptor tyrosine kinase binds to the receptor, it activates the downstream substrate to cause tyrosine phosphorylation and the signaling pathway [4]. Btk is involved in a variety of signaling pathways, such as mediating inflammatory responses and cell differentiation, and plays a more important role in B cell developmental tumors, rheumatoid arthritis, and X-linked agammaglobulinemia (XLA) [5]. PLCγ2 is a subtype of PLCγ, and activated PLCγ2 generates second messenger IP3 and DAG by hydrolyzing PIP2, thereby transferring extracellular information to downstream effector molecules in cells, and regulating
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