类风湿性关节炎(RA)是一种引起炎症的自身免疫性疾病,疼痛,最终,关节的骨侵蚀。这种疾病的原因是多方面的,包括遗传因素,例如存在人类白细胞抗原(HLA)-DRB1*04变体,微生物群的改变,或免疫因素,包括增加的细胞毒性T淋巴细胞(CTL),中性粒细胞,或M1巨噬细胞升高,放在一起,产生高水平的促炎细胞因子。在这次审查中,我们关注破骨细胞通过释放外泌体microRNAs(miRNA)对成骨细胞和其他破骨细胞的功能。在彻底修订的基础上,我们根据功能将这些分子分为三类:破骨细胞抑制剂(miR-23a,miR-29b,和miR-214),成骨细胞抑制剂(miR-22-3p,miR-26a,miR-27a,miR-29a,miR-125b,和miR-146a),和成骨细胞增强子(miR-20a,miR-34a,miR-96,miR-106a,miR-142,miR-199a,miR-324和miR-486b)。最后,我们分析了这些外泌体miRNA的潜在治疗靶点,例如使用antagomiRs,blockmiRs,agomiRs和竞争性内源性RNA(CERNA),已经在鼠类和体外RA模型中进行了测试。这些策略可能在重建破骨细胞和成骨细胞分化的调节方面发挥重要作用,从而在个性化医疗的发展中取得进展。
Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation, pain, and ultimately, bone erosion of the joints. The causes of this disease are multifactorial, including genetic factors, such as the presence of the human leukocyte antigen (HLA)-DRB1*04 variant, alterations in the microbiota, or immune factors including increased cytotoxic T lymphocytes (CTLs), neutrophils, or elevated M1 macrophages which, taken together, produce high levels of pro-inflammatory cytokines. In this review, we focused on the function exerted by osteoclasts on osteoblasts and other osteoclasts by means of the release of exosomal microRNAs (miRNAs). Based on a thorough revision, we classified these molecules into three categories according to their function: osteoclast inhibitors (miR-23a, miR-29b, and miR-214), osteoblast inhibitors (miR-22-3p, miR-26a, miR-27a, miR-29a, miR-125b, and miR-146a), and osteoblast enhancers (miR-20a, miR-34a, miR-96, miR-106a, miR-142, miR-199a, miR-324, and miR-486b). Finally, we analyzed potential therapeutic targets of these exosomal miRNAs, such as the use of
antagomiRs, blockmiRs, agomiRs and competitive endogenous RNAs (ceRNAs), which are already being tested in murine and ex vivo models of RA. These strategies might have an important role in reestablishing the regulation of osteoclast and osteoblast differentiation making progress in the development of personalized medicine.