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| Nhan đề : | Resolvin E1 Regulation of Osteoclast Precursors and Osteoclasts |
| Tác giả : | Van Dyke, Thomas Kantarci, Alpdogan Hasturk, Hatice Gallucci, German Han, Xiaozhe |
| Mô tả: | Inflammatory bone diseases are pathological conditions characterized by the loss of balance between bone resorption and bone formation. These pathologies typically occur when target tissues are infiltrated by macrophages, neutrophils, and T cells leading to chronic inflammatory response, activation of osteoclasts, distorted bone turnover and gradual bone loss. Complete resolution of inflammation, defined as the complete removal of inflammatory cells with return to homeostasis, is considered the ideal and optimum outcome of acute inflammation. Endogenous specialized proresolving mediators (SPMs) are a very critical class of inflammation resolution mediators and have a significant impact on wound healing. These local mediators are highly efficient in treating a number of inflammatory diseases in which inflammation plays a significant role in animal models. Previous studies have demonstrated that resolvins (Rv) directly interact with bone cells to exert their activity. RvE1 treatment of isolated osteoclasts reduces cell fusion in the late stages of osteoclast differentiation.
The purpose of this work was to establish RvE1 preventive regulation of osteoclasts in a ligature-induced alveolar bone loss disease model in mice and to investigate RvE1 regulation of bone marrow-derived osteoclast precursor and osteoclast differentiation through the BLT1 receptor. Moreover, we examined RvE1 regulation of osteoclast precursor and osteoclast proliferation, survival and apoptosis and the molecular signaling pathways involved.
Our investigations showed that RvE1 significantly reduced bone loss area (P<0.05) and volume (P<0.01) at the maxillary second molar furcation and number of mono- (P<0.01) and multi-nucleated (P<0.01) TRAP-stained osteoclasts along the entire length of the tooth in ligature-induced periodontal disease model in mice. Also, RvE1 significantly down-regulated gene expression of osteoclast markers (P<0.05) and hindered their differentiation (P<0.01) when induced at early osteoclast precursor (P<0.01) and late phases (P<0.01) in a dose-dependent manner. Moreover, BLT1 was revealed to be expressed on the cell surface of mice alveolar bone osteoclasts and bone marrow-derived osteoclast precursors and osteoclasts. Also, U75302-osteoclast cultures and U75302/RvE1-osteoclast cultures did not show any decrease in number of TRAP-stained multinucleated osteoclasts compared to control ones.
Proliferation and survival experiments showed that RvE1 significantly reduced osteoclast precursor and osteoclast proliferation (P<0.01) and viability (P<0.01) in a dose-dependent manner through BLT1 receptor. Also, RvE1 significantly increased osteoclast precursor and osteoclast apoptosis (P<0.01) through BLT1 receptor and significantly induced higher cleaved caspase 3 levels (P<0.01).
Finally, RvE1 demonstrated to induce significantly lower levels of phosphorylation of Akt (P<0.01) and to some extent ERK (P<0.01) when compared to control groups. Also, results obtained through using LTB4-, U75302-, wortmannin- and PD98059-induced osteoclast precursor and osteoclast cultures validated the Akt pathway for the RvE1-BLT1-Rac1 signaling and uncovered possible cross-talks between Akt and ERK as well as possible ERK inducing receptors and intracellular signaling molecules for RvE1 other than the BLT1-Rac1 pathway.
To conclude, RvE1 decreases bone loss and number of osteoclasts in vivo in a ligature-induced periodontal disease model in mice, prevents bone marrow-derived osteoclast precursor and osteoclast in vitro differentiation and reduces their proliferation and survival through attenuating the activation of the Akt signaling pathway. Oral Biology |
| URI: | http://lib.yhn.edu.vn/handle/YHN/208 |
| Định danh khác : | Marghalani, Amin A. 2019. Resolvin E1 Regulation of Osteoclast Precursors and Osteoclasts. Doctoral dissertation, Harvard School of Dental Medicine. http://nrs.harvard.edu/urn-3:HUL.InstRepos:42080563 |
| Bộ sưu tập | Y học |
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