Costa Viviana, De Fine Marcello, Carina Valeria, Conigliaro Alice, Raimondi Lavinia, De Luca Angela, Bellavia Daniele, Salamanna Francesca, Alessandro Riccardo, Pignatti Giovanni, Fini Milena, Giavaresi Gianluca
SC Scienze e Tecnologie Chirurgiche-SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Int J Mol Sci. 2021 Feb 28;22(5):2471. doi: 10.3390/ijms22052471.
Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of osteoblasts and chondrocytes genes expression, joint inflammation cytokines releases and cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA.
骨关节炎（OA）是一种涉及关节微观和宏观环境的退行性骨病。迄今为止，尚无针对OA的根治性治疗方法，新型疗法势在必行。最近的证据表明miRNA在OA进展中发挥作用。在我们之前的研究中，我们证明了miR-31-5p和miR-33a家族在不同骨再生信号传导中的作用。在此，我们研究了miR-31-5p和miR-33a-5p在OA进展中的作用。我们着重指出，根据不同的凯尔格伦和劳伦斯（KL）分级对OA患者关节组织分离出的成骨细胞和软骨细胞中miR-31-5p和miR-33a-5p的表达差异；并通过生物信息学方法鉴定了常见的miRNA靶标特异性蛋白（Sp1）。Sp1调节间隙连接蛋白连接蛋白43（Cx43）的表达，在OA中，Cx43驱动成骨细胞和软骨细胞基因表达的改变、关节炎症细胞因子的释放以及细胞功能。关于这一点，通过功能获得和丧失研究，还评估了Sp1作为通过miR-31-5p和miR-33a-5p作用调节CX43表达的调节剂的可能作用。最后，我们推测这两种miRNA共同调节成骨细胞和软骨细胞中SP1的表达，从而干扰CX43的表达，它们可能作为OA新的潜在生物标志物有待进一步研究。
