Selective Retinoic Acid Receptor γ Antagonist 7C is a Potent Enhancer of BMP-Induced Ectopic Endochondral Bone Formation.
Selective Retinoic Acid Receptor γ Antagonist 7C is a Potent Enhancer of BMP-Induced Ectopic Endochondral Bone Formation.
复制标题
DOI：
10.3389/fcell.2022.802699
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
Iwamoto M
中科院分区：
文献类型：
--
作者：
Tateiwa D;Kaito T;Hashimoto K;Okada R;Kodama J;Kushioka J;Bal Z;Tsukazaki H;Nakagawa S;Ukon Y;Hirai H;Tian H;Alferiev I;Chorny M;Otsuru S;Okada S;Iwamoto M
骨形态发生蛋白(BMPs)已被临床应用于肌肉骨骼疾病的骨形成诱导，如临界大小的骨缺损、骨不连和脊柱融合手术。然而，使用超生理学剂量的BMP会引起不良事件，有时甚至危及生命。因此，几十年来，人们一直在寻找更安全的骨再生治疗策略。全身性应用维甲酸核受体γ受体拮抗剂(RARγ)(7C)可促进骨形成蛋白诱导的异位骨形成。在这项研究中，我们开发了负载7C的聚乳酸纳米粒(7C-NPs)，并检测了局部应用7C是否促进了BMP诱导的骨再生。将吸附了重组人骨形态发生蛋白-2的胶原海绵圆盘植入幼年小鼠背筋膜内诱导异位骨。与单纯应用rhBMP-2相比，联合应用7C-NP能显著增加异位骨的总骨量和骨壳厚度，且呈剂量依赖关系。7C可刺激软骨细胞和MSCs硫酸蛋白多糖的产生、软骨形成标志物基因的表达和Sox9报告基因的活性。结果提示，选择性RAR7C或相关化合物可增强γ-2的骨诱导能力，并支持进一步安全有效地改进基于骨形态发生蛋白-2的骨再生过程的研究。
Bone morphogenetic proteins (BMPs) have been clinically applied for induction of bone formation in musculoskeletal disorders such as critical-sized bone defects, nonunions, and spinal fusion surgeries. However, the use of supraphysiological doses of BMP caused adverse events, which were sometimes life-threatening. Therefore, safer treatment strategies for bone regeneration have been sought for decades. Systemic administration of a potent selective antagonist of retinoic acid nuclear receptor gamma (RARγ) (7C) stimulated BMP-induced ectopic bone formation. In this study, we developed 7C-loaded poly lactic nanoparticles (7C-NPs) and examined whether local application of 7C enhances BMP-induced bone regeneration. The collagen sponge discs that absorbed recombinant human (rh) BMP-2 were implanted into the dorsal fascia of young adult mice to induce ectopic bone. The combination of rhBMP-2 and 7C-NP markedly increased the total bone volume and thickness of the bone shell of the ectopic bone in a dose-dependent manner compared to those with rhBMP-2 only. 7C stimulated sulfated proteoglycan production, expression of chondrogenic marker genes, and Sox9 reporter activity in both chondrogenic cells and MSCs. The findings suggest that selective RARγ antagonist 7C or the related compounds potentiate the bone inductive ability of rhBMP-2, as well as support any future research to improve the BMP-2 based bone regeneration procedures in a safe and efficient manner.
登录
查看更多内容
骨骼中的类视黄素受体及其在骨骼重塑中的作用。
影响因子：
5.2
作者：
Henning P;Conaway HH;Lerner UH
通讯作者：
Lerner UH
影响因子：
4.4
作者：
Dzhagalov, Ivan;Chambon, Pierre;He, You-Wen
通讯作者：
He, You-Wen
影响因子：
3.7
作者：
Chorny, Michael;Alferiev, Ivan S.;Fishbein, Ilia;Tengood, Jillian E.;Folchman-Wagner, Zoe;Forbes, Scott P.;Levy, Robert J.
通讯作者：
Levy, Robert J.
DOI：
10.1002/jbmr.2820
发表时间：
2016-09
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Chakkalakal SA;Uchibe K;Convente MR;Zhang D;Economides AN;Kaplan FS;Pacifici M;Iwamoto M;Shore EM
通讯作者：
Shore EM
影响因子：
5.3
作者：
Han, Yu;Lefebvre, Veronique
通讯作者：
Lefebvre, Veronique