Increased level of cell-derived microparticles in the cyst fluids of odontogenic keratocysts

Abstract

The aim of this study was to examine the level and basic characteristics of cell-derived microparticles (MPs) in the cyst fluids of odontogenic keratocysts (OKCs). For this purpose, MPs from the cyst fluids (CFMPs) of OKCs were purified by a classic differential centrifugation method and characterized by a transmission electron microscope and fluorescence microscope. Flow cytometric analysis was used to determine the size, concentration and cellular origins of the CFMPs. Moreover, the expression level of receptor activator for nuclear factor-κB ligand in the OKCs was evaluated by immunohistochemical staining and then analyzed for its correlation with the concentration of CFMPs by Spearman's rank correlation test. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and tartaric-resistant acid phosphatase (TRAP) staining were performed to examine the osteoclastogenesis of mouse bone marrow-derived macrophages (BMMs) in response to CFMPs. The results revealed that the levels of total CFMPs were significantly elevated in OKCs compared with dentigerous cysts (DCs) and radicular cysts (RCs). In addition, in vitro experiments further revealed that CFMPs derived from the OKCs of patients could be taken up by BMMs, leading to a significant increase in the mRNA expression levels of nuclear factor of activated T-cells 1 (NFATc1) and TRAP. Moreover, TRAP-positive multinucleated osteoclasts were successfully cultured in the presence of macrophage colony-stimulating factor (M-CSF) and CFMPs with BMMs. On the whole, our findings indicate that patients with OKCs have higher levels of CFMPs compared with patients with DCs and RCs, which may be associated with the bone resorption of OKCs.

Effect of Intracapsular Pressure on Decompression Effectiveness

“…Jaw cystic lesions can be developmental or inflammatory in origin, and lesion progression is closely related to intracapsular pressure and intracapsular-related factors. 13 , 14 , 15 Oka et al reported that positive pressure enhanced the expressions of IL-1α mRNA and protein in odontogenic keratocyte epithelial cells and increased the secretion of matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, and PGE2 in coculture; these factors are closely related to osteoclasts and are crucial for jaw cystic disease progression. 16 In our study, a significant positive correlation was observed between IL-1α concentration in the sac fluid and the intracapsular pressure.…”

Elevated ATF4 Expression in Odontogenic Keratocysts Epithelia: Potential Involvement in Tissue Hypoxia and Stromal M2 Macrophage Infiltration

“…2 On the contrary, one research from our group also used HIOECs to study the influence of cell-derived microparticles from the cyst fluids of OKC on the proliferation of epithelial cells in OKC. 29 However, OKCECs have been frequently found to be related to some gene mutations, including oncogenic PTCH, L-MYC, CMN, and VHL, 30 which indicated that OKCECs are different from HIOECs in the genetic background. Therefore, although our data in vitro implicated the role of hypoxia on the expressions of ATF4 and M-CSF in epithelial cells, studies using OKCECs are still needed to strengthen the in vitro findings of this study in the future.In conclusion, the present study showed the accumulation of ATF4 in the epithelium of OKC, and its potential association with M2-polarized macrophages infiltration and angiogenesis.…”