IL-36 Induces Bisphosphonate-Related Osteonecrosis of the Jaw-Like Lesions in Mice by Inhibiting TGF-β-Mediated Collagen Expression.
IL-36 Induces Bisphosphonate-Related Osteonecrosis of the Jaw-Like Lesions in Mice by Inhibiting TGF-β-Mediated Collagen Expression.
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DOI：
10.1002/jbmr.2985
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Kim RH
中科院分区：
文献类型：
--
作者：
Kim S;Williams DW;Lee C;Kim T;Arai A;Shi S;Li X;Shin KH;Kang MK;Park NH;Kim RH
长期使用含氮双膦酸盐可引起人类双膦酸盐相关性颌骨骨坏死（BRONJ）等有害副作用。虽然已知炎症与BRONJ的发展有关，但详细的潜在机制尚不清楚。在这里，我们报告了促炎细胞因子IL-36α在一定程度上负责BRONJ的发展。我们发现小鼠BRONJ病变中IL-36α水平明显升高，胶原蛋白水平明显降低。我们还发现IL-36α通过激活Erk信号通路显著抑制TGF-β介导的小鼠牙龈间充质干细胞中colα 1和α-Sma的表达。当体内IL-36信号被消除时，小鼠BRONJ病变的发展得到改善。综上所述，我们发现IL-36α通过抑制胶原表达在BRONJ发展中的病理作用，并证明IL-36α可能是预防和治疗BRONJ的潜在标记物和治疗靶点。
Long-term administration of nitrogen-containing bisphosphonates can induce detrimental side effects such as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in human. Although inflammation is known to be associated with BRONJ development, the detailed underlying mechanism remains unknown. Here, we report that the pro-inflammatory cytokine IL-36α is, in part, responsible for the BRONJ development. We found a notably higher level of IL-36α and lower level of collagen in the BRONJ lesions in mice. We also found that IL-36α remarkably suppressed TGF-β-mediated expression of Collα1 and α-Sma via the activation of Erk signaling pathway in mouse gingival mesenchymal stem cells. When IL-36 signaling was abrogated in vivo, development of BRONJ lesions was ameliorated in mice. Taken together, we showed the pathologic role of IL-36α in BRONJ development by inhibiting collagen expression and demonstrated that IL-36α could be a potential marker and a therapeutic target for the prevention and treatment of BRONJ.
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DOI：
10.4049/jimmunol.1301481
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Foster AM;Baliwag J;Chen CS;Guzman AM;Stoll SW;Gudjonsson JE;Ward NL;Johnston A
通讯作者：
Johnston A
影响因子：
8
作者：
通讯作者：
--
影响因子：
3
作者：
Kursunlu, Sabri Fatih;Ozturk, Veli Ozgen;Emingil, Gulnur
通讯作者：
Emingil, Gulnur
影响因子：
7.6
作者：
Mawardi, H.;Giro, G.;Kawai, T.
通讯作者：
Kawai, T.
影响因子：
6.2
作者：
Luckman, SP;Hughes, DE;Rogers, MJ
通讯作者：
Rogers, MJ