How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights

被引:14
|
作者
Costa, Viviana [1 ]
De Fine, Marcello [2 ]
Carina, Valeria [1 ]
Conigliaro, Alice [3 ]
Raimondi, Lavinia [1 ]
De Luca, Angela [1 ]
Bellavia, Daniele [1 ]
Salamanna, Francesca [1 ]
Alessandro, Riccardo [3 ,4 ]
Pignatti, Giovanni [2 ]
Fini, Milena [1 ]
Giavaresi, Gianluca [1 ]
机构
[1] IRCCS Ist Ortoped Rizzoli, SC Sci & Tecnol Chirurg, SS Piattaforma Sci Om Ortopedia Personalizzata, I-40136 Bologna, Italy
[2] IRCCS Ist Ortoped Rizzoli, I-40136 Bologna, Italy
[3] Univ Palermo, Sect Biol & Genet, Dept Biomed Neurosci & Adv Diagnost BiND, I-90133 Palermo, Italy
[4] Ist Ric & Innovaz Biomed IRIB, I-90133 Palermo, Italy
关键词
osteoarthritis; microRNAs; osteoblasts; chondrocytes; SP1; CX43;
D O I
10.3390/ijms22052471
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (i) osteoblasts and chondrocytes genes expression, (ii) joint inflammation cytokines releases and (iii) 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.
引用
收藏
页码:1 / 16
页数:15
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